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Biophysical Chemistry

Current research reports and chronological list of recent articles..




The scientific journal Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.

The publisher is Elsevier. The copyright and publishing rights of specialized products listed below are in this publishing house. This is also responsible for the content shown.

To search this web page for specific words type "Ctrl" + "F" on your keyboard (Command + "F" on a Mac). Then: type the word you are searching for in the window that pops up!

Additional research articles see Current Chemistry Research Articles. Magazines with similar content (biophysical chemistry):

 - Biomacromolecules.

 - Faraday Discussions.

 - Journal of Physical Chemistry B.

 - Physical Chemistry Chemical Physics PCCP.



Biophysical Chemistry - Abstracts



How the dyes affect folding of small proteins in single-molecule FRET experiments: A simulation study

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Sergei F. Chekmarev

Abstract

A key question in the application of the single-molecule Förster resonance energy transfer (smFRET) technique to study protein folding is how the dyes affect the protein behavior. Understanding of these effects is particularly important for small proteins, for which the dyes, along with their linkers, can be comparable in size (mass) with the protein. Using a coarse-grained model, we simulated folding of BBL protein and two of its FRET constructs. The obtained results suggest that even for small proteins, such as the 45-residue BBL, the appearance of the excluded volume in the protein conformation space due to the presence of dyes does not change the overall picture of folding. At the same time, some deviations from folding of the original protein are observed, in particular, the FRET constructs fold considerably slower than the original protein because the protein collapse in the initial state of folding is slowed down due to the protein loading with relatively massive dyes.

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Biophysical modeling of β-cells networks: Realistic architectures and heterogeneity effects

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): A. Loppini, L. Chiodo

Abstract

The β-cells dynamics is the regulator of insulin secretion in the pancreas, and its investigation is a central aspect in designing effective treatment strategies for diabetes. Despite great efforts, much is still unknown about the complex organization of such endocrine cells and realistic mathematical modeling represents a useful tool to elucidate key aspects of glucose control in humans. In this contribution, we study the human β-cells collective behaviour, by modeling their electric and metabolic coupling in a cluster, of size and architecture similar to human islets of Langerhans. We focus on the effect of coupling on various dynamics regimes observed in the islets, that are spiking and bursting on multiple timescales. In particular, we test the effect of hubs, that are highly glucose-sensitive β-cells, on the overall network dynamics, observing different modulation depending on the timescale of the dynamics. By properly taking into account the role of cells heterogeneity, recently emerged, our model effectively describes the effect of hubs on the synchronization of the islet response and the correlation of β-cells activity.

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Identifying necessary and sufficient conditions for the observability of models of biochemical processes

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Paola Lecca, Angela Re

Abstract

The notions of observability and controllability of non-linear systems are a cornerstone of mathematical control theory and cover a wide scope of applications including process design, characterization, monitoring and control. Synthetic biology - which aims to (re)-program living functionalities - and bio-based process engineering - which aims to develop biotechnological manufacturing processes based on industrial and natural living agents - remarkably benefit of methodological improvements inspired to control theory for countless reasons including the huge variety of control mechanisms in living organisms, experimental limitations in terms of measurement feasibility, design of controllers - at single cell or population level - of synthetic production processes and process optimization purposes. Many fundamental problems of control theory such as stabilisability of unstable systems and optimal control may be solved under the assumption that the system is observable/controllable. Observability and controllability are mathematical duals, that means that the observability property can be determined analysing the controllability of the dual system and vice versa. Given this duality, we focus on observability. In this work, we revisit a generalization of the Fujisawa and Kuh theorem as a tool to explore the possibility that a system is observable. We show that the theorem, when applicable, is a sufficient but not necessary condition for observability. We revisit the theorem to propose a necessary and sufficient condition for observability for non-linear systems. Finally, we show how it is possible to identify regions of the phase space of the model in which the model is observable.

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Symmetrical interactions in K+ channel

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Yuval Ben-Abu

Abstract

Potassium channels open and close their pore in response to changes in chemical or electrical potential. This process, referred to as gating, results from mechanical coupling of gating domain movements to pore opening and closing and is fundamental in many biological processes including, in particular, electrical signaling in the nervous system. Although, in general, the pore-opening mechanics of K+ channels are conserved in voltage- and ligand-gated channels, it is still not clear for many K+ channels whether gating domains exert positive work to open or to close the pore. This question is related to the intrinsic stability of the pore domain: provided the pore domain of a K+ channel is detached from its gating domains, will it stay closed or open? What factors determine the pore's thermodynamic intrinsic stability? An important hint is provided here upon sequence comparisons of two families of K+ channel families, the voltage activated K+ channel and the leak K2P channel family, demonstrating opposing pore stability phenotypes. Whereas the activation gate region of the voltage-gated K+ channel family is spanned, primarily, by large and b-branched hydrophobic residues, the leak K2P channel activation gate is spanned mainly by glycines and other hydrophilic residues. These differences might explain why in the voltage-gated potassium channel family, the closed pore conformation is intrinsically more stable, whereas in the leak background K+ channel family it is the open one which is probably intrinsically more stable. This observation leads to the hypothesis that hydrophobic interactions at the activation gates of K+ channels play a crucial role in modulating pore stability and, hence, channel gating.


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Self-crowding influences the temperature – pressure stability of the human telomere G-quadruplex

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): J. Somkuti, M. Adányi, L. Smeller

Abstract

We measured the effect of crowded environment on G-quadruplex structures, formed by guanine rich DNA sequences. Fluorescence and infrared spectroscopy were used to determine the temperature stability of G-quadruplex structure formed by the human telomere sequence. We determined the T-p phase diagram of Htel aptamer up to 1 GPa at different self-crowding conditions. The unfolding volume change was determined from the pressure induced shift of the unfolding temperature of the quadruplex form. The unfolding volume change decreased in magnitude, and even its sign changed from negative (−19 ml/mol) to positive (7 ml/mol) under self-crowded conditions. The possible explanations are the appearance of the parallel GQ structure at high concentration or the fact that the volume decrease caused by the released central K+ ion during the unfolding is less significant in crowded environment.

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Meso-Raman approach for rapid yeast cells identification

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Martina Alunni Cardinali, Debora Casagrande Pierantoni, Silvia Caponi, Laura Corte, Daniele Fioretto, Gianluigi Cardinali

Abstract

An increasing effort is currently devoted to developing Raman spectroscopy for identification of microorganisms. Micro-Raman setups are typically used for this purpose with the limit that the intra-species and inter-species spectral variability are comparable, thus limiting the identification capability. To overcome this limit a meso-Raman approach is here implemented. Thin films of planktonic cells are analyzed throughout the collection of back-scattered light providing a Raman signal already averaged over tens of cells. The collecting of unpolarized (VU) and depolarized (HV) Raman signals increased the spectral information obtainable from the data, demonstrating the ability of the principal component analysis to differentiate the most common Candida species, namely C. glabrata, C. albicans, C. parapsilosis and C. tropicalis. The proposed method can contribute to bring Raman spectroscopy closer to its potential clinical use for fast identification of yeast cells.

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An equation for biomimicking macromolecular crowding using <em>Escherichia coli</em> MG1655 strain

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Khushal Khambhati, Nisarg Gohil, Gargi Bhattacharjee, Happy Panchasara, Vijai Singh

Abstract

Macromolecules present in the intracellular environment of a cell are densely packed, resulting in a highly crowded cytosolic environment. This crowded milieu influences several biochemical equilibria such as diffusibility and association constant of biomolecules which impose a serious impact on cellular functions as well as its processes. A number of in silico and in vitro studies have been reported till date about using synthetic crowding agents for resembling such a crowding environment within the cell. Lately, it has been realized that synthetic crowders are not suitable for mimicking the intrinsic environment of the cell. In this study, proteins were assumed to be the major biological molecule which contributes to the crowding environment. We have semi-theoretically determined the total protein concentration within an individual E. coli MG1655 cell which changes notably as the growth curve proceeds from 0.2 to 1.0 OD600. The average range of total cellular protein concentration throughout the batch culture was found to be in the range of 15.2 to 178 fg/fL of cytoplasmic volume. The fundamental knowledge gained through the study was translated to applied research in the form of an equation. We propose an equation that could help to mimic the OD600 dependent crowding environment present within a single cell of E. coli in the desired volume of reaction solution. In a nutshell, the equation provides quantitative estimation of the volume of culture required to prepare the cell lysate for biomimicking the intracellular crowding environment in vitro. This finding provides a new insight into the cellular cytosolic environment that could be used as a platform to frame more cells like environment in cell-free protein synthesis (CFPS) system for synthetic biology applications.

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Macromolecules present in the intracellular environment of a cell are densely packed, resulting in a highly crowded cytosolic environment. This crowded milieu influences several biochemical equilibria such as diffusibility and association constant of biomolecules which impose a serious impact on cellular functions as well as its processes. A number of in silico and in vitro studies have been reported till date about using synthetic crowding agents for resembling such a crowding environment within the cell. Schematic representation of an approach for calculating the OD600 dependent total protein concentration found within a cell of E. coli MG1655 and development of an equation for biomimicking that particular concentration in vitro. (1) Indicates a densely packed cytosolic milieu of a cell. (2) The E. coli MG1655 cells were cultured and the protein biomass was quantified as per OD600 dependent manner. Dividing the total protein biomass quantified, by the number of cells present in the sample gives the protein biomass contributed by an individual cell. Dividing the obtained biomass by the OD600 dependent cellular volume gives the total protein concentration present within a cell. (3) The data obtained was used for deriving an equation which assists to determine either the buffer volume that is required to resuspend the cultured cell pellet for lysate preparation, or to know the volume of the cultured cell that is to be harvested for preparing a particular volume of cell lysate. In either way, the end result would demonstrate the crowding that could be present within an individual cell of E. coli in the desired volume of lysate solution (4) The criteria for validation of the derived equation. If the cell lysate that has been prepared experimentally using the derived equation contains the protein biomass close to the quantity estimated by theoretical calculation then the equation works well. (5) The resultant solution would resemble the crowded environment found within a cell.

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Label-free, real-time on-chip sensing of living cells via grating-coupled surface plasmon resonance

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Giulia Borile, Stefano Rossi, Andrea Filippi, Enrico Gazzola, Pietro Capaldo, Claudia Tregnago, Martina Pigazzi, Filippo Romanato

Abstract

The application of nanotechnologies to address biomedical questions is a key strategy for innovation in biomedical research. Among others, a key point consists in the availability of nanotechnologies for monitoring cellular processes in a real-time and label-free approach. Here, we focused on a grating-coupled Surface Plasmon Resonance (GC-SPR) sensor exploiting phase interrogation. This sensor can be integrated in a microfluidic chamber that ensures cell viability and avoids cell stress. We report the calibration of the sensor response as a function of cell number and its application to monitor cell adhesion kinetics as well as cell response to an external stimulus. Our results show that GC-SPR sensors can offer a valuable alternative to prism-coupled or imaging SPR devices, amenable for microfluidic implementation.

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The pressure and temperature perturbation approach reveals a whole variety of conformational substates of amyloidogenic hIAPP monitored by 2D NMR spectroscopy

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Markus Beck Erlach, Hans Robert Kalbitzer, Roland Winter, Werner Kremer

Abstract

The intrinsically disordered human islet amyloid polypeptide (hIAPP) is a 37 amino acid peptide hormone that is secreted by pancreatic beta cells along with glucagon and insulin. The glucose metabolism of humans is regulated by a balanced ratio of insulin and hIAPP. The disturbance of this balance can result in the development of type-2 diabetes mellitus (T2DM), whose pathogeny is associated by self-assembly induced aggregation and amyloid deposits of hIAPP into nanofibrils. Here, we report pressure- and temperature-induced changes of NMR chemical shifts of monomeric hIAPP in bulk solution to elucidate the contribution of conformational substates in a residue-specific manner in their role as molecular determinants for the initial self-assembly. The comparison with a similar peptide, the Alzheimer peptide Aβ(1–40), which is leading to self-assembly induced aggregation and amyloid deposits as well, reveals that in both peptides highly homologous areas exist (Q10–‍L16 and N21–L27 in hIAPP and Q15–A21 and S26–I32 in Aβ). The N-terminal area of hIAPP around amino acid residues 3–20 displays large differences in pressure sensitivity compared to Aβ, pinpointing to a different structural ensemble in this sequence element which is of helical origin in hIAPP. Knowledge of the structural nature of the highly amyloidogenic hIAPP and the differences with respect to the conformational ensemble of Aβ(1–40) will help to identify molecular determinants of self-assembly as well as cross-seeded assembly initiated aggregation and help facilitate the rational design of drugs for therapeutic use.

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Urea's match in the hydrogen-bond network? A high pressure THz study

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Hendrik Vondracek, Serena Alfarano, Claudius Hoberg, Inga Kolling, Fabio Novelli, Federico Sebastiani, Jean-Blaise Brubach, Pascale Roy, Gerhard Schwaab, Martina Havenith

Abstract

We present results of the measurement of the low frequency spectrum of solvated urea. The study revealed a blue shift of the intramolecular mode of urea centered at 150 cm−1 of Δν= 17 cm−1 upon increasing the pressure up to 10 kbar. The blue shift scaled linearly with the increase in density and was attributed to a stiffening of the water-urea intermolecular potential. We deduced an increase in the number of affected water molecules from 1 to 2 up to 5–7, which corresponds to the sterical coordination number of urea. The increase in hydration number can be explained by an suppression of the NH2 inversion and the hydrogen bond switching around the NH2 group. Pressure induced sterical constraints are proposed to hinder the rapid switching of hydrogen bond partners and make the water around urea less bulk-like than under ambient conditions.

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Apomyoglobin is an efficient carrier for zinc phthalocyanine in photodynamic therapy of tumors

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Marco Cozzolino, Luca Pesce, Denise Pezzuoli, Chiara Montali, Lorenzo Brancaleon, Luigi Cavanna, Stefania Abbruzzetti, Alberto Diaspro, Paolo Bianchini, Cristiano Viappiani

Abstract

The spectral and the photophysical properties of phthalocyanines have made these dyes attractive for applications in photodynamic therapy of cancer. One important known issue of these compounds is their tendency to aggregate in aqueous media, which decreases their fluorescence, triplet, and singlet oxygen quantum yields. We report on the use of apomyoglobin as a carrier for zinc phthalocyanine (ZnPc) to overcome solubility limitations of the dye. We show that the protein is able to bind ZnPc in monomeric form, preserving its photophysics. Confocal fluorescence imaging of PC3 and HeLa cells, treated with the complex between ZnPc and apomyoglobin, demonstrates that the photosensitizer is uptaken quickly by cells. Illumination of treated cells strongly decreases viability, as demonstrated by live/dead fluorescence assay.

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High pressure response of <sup>1</sup>H NMR chemical shifts of purine nucleotides

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Claudia E. Munte, Matthias Karl, Waldemar Kauter, Lukas Eberlein, Thuy-Vy Pham, Markus Beck Erlach, Stefan M. Kast, Werner Kremer, Hans Robert Kalbitzer

Abstract

The study of the pressure response by NMR spectroscopy provides information on the thermodynamics of conformational equilibria in proteins and nucleic acids. For obtaining a database for expected pressure effects on free nucleotides and nucleotides bound in macromolecular complexes, the pressure response of 1H chemical shifts and J-coupling constants of the purine 5′-ribonucleotides AMP, ADP, ATP, GMP, GDP, and GTP were studied in the absence and presence of Mg2+-ions. Experiments are supported by quantum-chemical calculations of populations and chemical shift differences in order to corroborate structural interpretations and to estimate missing data for AMP. The preference of the ribose S puckering obtained from the analysis of the experimental J-couplings is also confirmed by the calculations. In addition, the pressure response of the non-hydrolysable GTP analogues GppNHp, GppCH2p, and GTPγS was examined within a pressure range up to 200 MPa. As observed earlier for 31P NMR chemical shifts of these nucleotides the pressure dependence of chemical shifts is clearly non-linear in most cases. In di- and tri-phospho nucleosides, the resonances of the two protons bound to the ribose 5′ carbon are non-equivalent and can be observed separately. The gg-rotamer at C4′- C5′ bond is strongly preferred and the downfield shifted resonance can be assigned to the H5″ proton in the nucleotides. In contrast, in adenosine itself the frequencies of the two resonances are interchanged.

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Structural analysis of the transferrin receptor multifaceted ligand(s) interface

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Claudia Testi, Alberto Boffi, Linda Celeste Montemiglio

Abstract

The transferrin receptor 1 (TfR1) is one of the key regulators of iron homeostasis for most higher organisms. It mediates cellular iron import through a constitutive clathrin-dependent endocytosis mechanism and by recruiting iron- regulator proteins as transferrin, Hereditary Hemochromatosis factor (HFE) and serum ferritin in response to cellular demand. The receptor is also opportunistically exploited by several viruses and the malaria parasite as a preferential door for cell invasion. In this review, we analyze the structural information available for TfR1 and all its functional complexes to figure out how structural signals in a single receptor can guide the recognition of multiple ligands and how the conservation of key residues in TfR1 might have a role in iron uptake and cell infection.

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Structure and thermodynamics of aqueous urea solutions from ambient to kilobar pressures: From thermodynamic modeling, experiments, and first principles simulations to an accurate force field description

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): Christoph Hölzl, Patrick Kibies, Sho Imoto, Jan Noetzel, Michael Knierbein, Paul Salmen, Michael Paulus, Julia Nase, Christoph Held, Gabriele Sadowski, Dominik Marx, Stefan M. Kast, Dominik Horinek

Abstract

Molecular simulations based on classical force fields are a powerful method for shedding light on the complex behavior of biomolecules in solution. When cosolutes are present in addition to water and biomolecules, subtle balances of weak intermolecular forces have to be accounted for. This imposes high demands on the quality of the underlying force fields, and therefore force field development for small cosolutes is still an active field. Here, we present the development of a new urea force field from studies of urea solutions at ambient and elevated hydrostatic pressures based on a combination of experimental and theoretical approaches. Experimental densities and solvation shell properties from ab initio molecular dynamics simulations at ambient conditions served as the target properties for the force field optimization. Since urea is present in many marine life forms, elevated hydrostatic pressure was rigorously addressed: densities at high pressure were measured by vibrating tube densitometry up to 500 bar and by X-ray absorption up to 5 kbar. Densities were determined by the perturbed-chain statistical associating fluid theory equation of state. Solvation properties were determined by embedded cluster integral equation theory and ab initio molecular dynamics. Our new force field is able to capture the properties of urea solutions at high pressures without further high-pressure adaption, unlike trimethylamine-N-oxide, for which a high-pressure adaption is necessary.

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Simultaneous multisite detection of quantal release from PC12 cells using micro graphitic-diamond multi electrode arrays

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Giulia Tomagra, Claudio Franchino, Alberto Pasquarelli, Emilio Carbone, Paolo Olivero, Valentina Carabelli, Federico Picollo

Abstract

Micro graphitic – diamond – multi electrode arrays (μG-D-MEAs) are suitable for measuring multisite quantal dopamine (DA) release from PC12 cells. Following cell stimulation with high extracellular KCl and electrode polarization at +650 mV, amperometric spikes are detected with a mean frequency of 0.60 ± 0.16 Hz. In each recording, simultaneous detection of secretory events is occurred in approximately 50% of the electrodes. Kinetic spike parameters and background noise are preserved among the different electrodes. Comparing the amperometric spikes recorder under control conditions with those recorders from PC12 cells previously incubated for 30 min with the dopamine precursor Levodopa (L-DOPA, 20 μM) it appears that the quantal size of amperometric spikes is increased by 250% and the half-time width (t1/2) by over 120%. On the contrary, L-DOPA has no effect on the frequency of secretory events.

Overall, these data demonstrate that the μG-D-MEAs represent a reliable bio-sensor to simultaneously monitor quantal exocytotic events from different cells and in perspective can be exploited as a drug-screening tool.

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Amyloid jams: Mechanical and dynamical properties of an amyloid fibrillar network

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Vincenzo Martorana, Samuele Raccosta, Daniela Giacomazza, Lorena Anna Ditta, Rosina Noto, Pier Luigi San Biagio, Mauro Manno

Abstract

Amyloid fibrils have well known pathological implications as well as a clear functional role in different biological systems due to their peculiar structural and mechanical properties. We had previously shown the appearance of elastic properties during the formation of a gel of insulin amyloid fibrils. Here, we study the morphological, rheological and dynamical behaviour of this jammed system. We observe different non-diffusive relaxation processes over a wide length and time interval, suggesting the formation of an elastic transient network of fibrils, and evidencing the structural heterogeneity of the gel matrix and the peculiarity of this potentially new material.

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The quaternary structure of insulin glargine and glulisine under formulation conditions

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Norbert Nagel, Melissa A. Graewert, Mimi Gao, Winfried Heyse, Cy M. Jeffries, Dmitri Svergun, Harald Berchtold

Abstract

The quaternary structures of insulin glargine and glulisine under formulation conditions and upon dilution using placebo or water were investigated using synchrotron small-angle X-ray scattering. Our results revealed that insulin glulisine in Apidra® is predominantly hexameric in solution with significant fractions of dodecamers and monomers. Upon dilution with placebo, this equilibrium shifts towards monomers. Insulin glargine in Lantus® and Toujeo® is present in a stable hexamer/dimer equilibrium, which is hardly affected by dilution with water down to 1 mg/ml insulin concentration. The results provide exclusive insight into the quaternary structure and thus the association/dissociation properties of the two insulin analogues in marketed formulations.

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Interdigitated lamellar phases in the frozen state: Spin-label CW- and FT-EPR

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Erika Aloi, Rosa Bartucci

Abstract

Interdigitated lamellar phases composed of dipalmitoylphosphatidylcholine (DPPC) and equimolar content of lyso-palmitoylphosphatidylcholine (Lyso-PPC) or DPPC hydrated in ethanol containing water (60% v/v) have been studied in the frozen state. Electron paramagnetic resonance spectra of labeled lipids at C5 or C16 carbon atom positions along the chain are indicative of segmental librational motion over the temperature range 120–260 K. For any dispersion, the mean-square-angular amplitudes of the librations are comparable for both label positions but are larger in DPPC/etOH than in DPPC/Lyso-PPC interdigitated sample. The temperature dependences of the librational amplitudes of the labels in the lipid matrices show a rapid increase at the dynamical transition at Td ≈ 220 K with an activation energy of 20–30 kJ/mol. Three-pulse electron spin echo envelope modulation by D2O revealed comparable solvent accessibility and fractions of singly and doubly hydrogen-bonded nitroxides to deuterons for both positional isomers in the interdigitated lamellae at 77 K. The overall EPR results indicate that the interdigitated DPPC/etOH sample is more loosened packed compared to DPPC/Lyso-PPC sample. The findings of the present work obtained at cryogenic temperatures point out dynamic and molecular properties of interdigitated lamellae that contribute to the biophysical characterization of membrane model systems.

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Incorporating phototransduction proteins in zebrafish green cone with pressure-polished patch pipettes

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Marco Aquila, Daniele Dell'Orco, Ramona Fries, Karl-Wilhelm Koch, Giorgio Rispoli

Abstract

The neuronal Ca2+-sensor guanylate cyclase-activating protein 3 (zGCAP3) is a major regulator of guanylate cyclase (GC) activity expressed in zebrafish cone cells. Here, the zGCAP3, or a monoclonal antibody directed against zGCAP3, was injected in the cone cytoplasm by employing the pressure-polished pipette technique. This technique allows to perform “real time” zGCAP3 (or of any other phototransduction protein) over-expression or knock-down, respectively, via the patch pipette. Photoresponses were not affected by purified zGCAP3, indicating that GC was already saturated with endogenous zGCAP3. The cytosolic injection of anti-zGCAP3 produced the slowing down kinetics of the flash response recovery, as theoretically expected by a minimal phototransduction model considering the antibody acting exclusively on the maximal GC activation by low Ca2+. However, the antibody produced a progressive current decay toward the zero level, as if the antibody affected also the basal GC activity in the dark.

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Insight on collagen self-assembly mechanisms by coupling molecular dynamics and UV spectroscopy techniques

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Ludovica Leo, Maria Grazia Bridelli, Eugenia Polverini

Abstract

Self-assembly of rat tail collagen type I was investigated by means of turbidity measurements and molecular dynamics simulations. Turbidity curves collected at different pH values show that the rate of aggregation was not linear in dependence from pH, with the fastest kinetics at pH 5.0 and the lowest at neutral pH. MD simulations were carried out on two regions with different hydropathicity, monitoring the aggregation of up to four staggered tropocollagen fragments at different ionic strength. At physiological conditions, association of lowly charged regions occurs more easily than for highly charged ones, the latter seeming to aggregate in a sequential way. The first contacts indicate for both regions that the driving force is hydrophobic, the electrostatic contribution becoming relevant at short distance. The direct inter-tropocollagen H-bonds confirm that fibrillogenesis is driven by loss of surface water from the monomers and involves in large percentage hydroxyproline residues. Low ionic strength dynamics leads to the formation of incorrect assemblies, driven by not shielded pairwise charge interactions.

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A perspective on the modulation of plant and animal two pore channels (TPCs) by the flavonoid naringenin

Publication date: November 2019

Source: Biophysical Chemistry, Volume 254

Author(s): D. Benkerrou, V. Minicozzi, A. Gradogna, S. Milenkovic, I.V. Bodrenko, M. Festa, L. Lagostena, L. Cornara, A. D'Amore, M. Ceccarelli, A. Filippini, A. Carpaneto

Abstract

The inhibitory effect of the flavonoid naringenin on plant and human Two-Pore Channels (TPCs) was assessed by means of electrophysiological measurements. By acting on human TPC2, naringenin, was able to dampen intracellular calcium responses to VEGF in cultured human endothelial cells and to impair angiogenic activity in VEGF-containing matrigel plugs implanted in mice. Molecular docking predicts selective binding sites for naringenin in the TPC structure, thus suggesting a specific interaction between the flavonoid and the channel.

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Density variations of TMAO solutions in the kilobar range: Experiments, PC-SAFT predictions, and molecular dynamics simulations

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Michael Knierbein, Christoph Held, Christoph Hölzl, Dominik Horinek, Michael Paulus, Gabriele Sadowski, Christian Sternemann, Julia Nase

Abstract

We present measurements, molecular dynamics (MD) simulations, and predictions using Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) of the density of aqueous solutions in a pressure range from 1 bar to 5000 bar, a pressure regime that is highly relevant for both biochemical applications and the fundamental understanding of solvation. The accurate determination of density data of pressurized solutions remains challenging. We determined relative density changes from the variations in X-ray absorption through the sample and developed a new water parameter set for PC-SAFT modeling that is appropriate for high pressure conditions in the kilobar regime. As a showcase, we studied trimethylamine N-oxide (TMAO) solutions and demonstrated that their compressibility decreases with the TMAO content. This result is linked to the stabilizing effect of TMAO on the local H-bond network of water. Experiments and calculations, which represent two independent methods, are in very good agreement and are in accordance with results of force field molecular dynamics simulations of the same systems.

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Thermodynamic properties of aqueous osmolyte solutions at high-pressure conditions

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Michael Knierbein, Maximilian Venhuis, Christoph Held, Gabriele Sadowski

Abstract

Living organisms can be encountered in nature under extreme conditions. At the seabed, pressure may reach 1000 bar. Yet microorganisms can be found that still function under these conditions. On the one hand, it is known that high pressure even has a positive effect on piezophile enzymes increasing their activity. On the other hand, such microorganisms might contain up to very high concentrations of osmolytes that counteract osmotic stress. To better understand high-pressure influences on biochemical systems, fundamental knowledge about pressure effects on thermodynamic properties of such osmolytes is important. However, literature data is scarce and experiments at high-pressure conditions are challenging. Hence, new high-pressure density data of aqueous osmolyte solutions were measured in this work at temperatures between 298.15 K and 318.15 K and at osmolyte concentrations up to 3 mol/kg water. Further, the thermodynamic model PC-SAFT has been applied recently to successfully model vapor pressures of water and density of water up to 10 kbar [M. Knierbein et al., Density variations of TMAO solutions in the kilobar range: experiments, PC-SAFT predictions, and molecular dynamics simulations, Biophysical chemistry, (2019)]. This allowed accurately predicting effects of temperature and osmolyte concentration on thermodynamic properties (especially mixture densities) up to very high pressures. Common osmolytes (trimethylamine-N-oxide, urea, ectoine, glycerol, glycine) as well as the dipeptides acetyl-N-methylglycine amide, acetyl-N-methylalanine amide, and acetyl-N-methylleucine amide were under investigation.

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Structure-based derivation and intramolecular cyclization of peptide inhibitors from PD-1/PD-L1 complex interface as immune checkpoint blockade for breast cancer immunotherapy

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Kun Zhou, Ji Lu, Xiaoxin Yin, Han Xu, Longzhi Li, Baojin Ma

Abstract

The interaction event between programmed death receptor-1 (PD-1) and its ligand (PD-L1) functions as an essential immune checkpoint against cytotoxic T effector cell activation. Previously, a number of small-molecule inhibitors and antibody drugs have been successfully developed to block the PD1/PDL1 signaling axis for breast cancer immunotherapy. Here, we attempt to directly disrupt the formation of PD-1/PD-L1 complex by using a self-inhibitory peptide (SIP) strategy. In the procedure, the complex crystal structure is examined systematically with energetic analysis and alanine scanning. Two double-stranded segments I and II in PD-L1 active finger are identified as hotspot regions; they directly interact with the amphipathic pocket of PD-1 to form the complex system. The segments are derived from PD-L1 to define two SIP peptides, namely, DS-I and DS-II, which are thought to have capability of rebinding at the complex interface, thus disrupting PD-1/PD-L1 interaction as a new immune checkpoint blockade. A further analysis reveals that the free linear DS-I and DS-II peptides are highly flexible without protein context support, which would incur a large entropy penalty (unfavorable indirect readout effect) when rebinding to PD-1. Next, intramolecular cyclization is applied to constraining the intrinsically disordered conformation of free DS-II peptide into native ordered double-stranded configuration, which can be substantiated by molecular dynamics simulation and circular dichroism spectroscopy. Several cyclized counterparts of linear DS-II peptide are designed and their affinities to PD-1 are determined using fluorescence polarization assays. As might be expected, three designed cyclic peptides DS-II[c111–127], ΔDS-II[c111–127] and ΔDS-II[c110–128] exhibit considerably increased potency (Kd = 28.0 ± 4.2, 17.5 ± 3.1 and 11.6 ± 2.3 μM, respectively) relative to linear DS-II peptide (Kd = 109 ± 15 μM).

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Fluorescence correlation spectroscopy as a tool for the study of the intracellular dynamics and biological fate of protein corona

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Marta Martinez-Moro, Desiré Di Silvio, Sergio E. Moya

Abstract

In biological fluids, nanoparticles (NPs) are in contact with proteins and other biomolecules. Proteins adsorb to NPs and form a coating called a protein corona (PC). The PC is known to greatly affect the interaction of NPs with biological systems. A comprehensive knowledge of the protein nanoparticle interaction is essential to understand the biological fate of NPs and for the design of NPs for biomedicine. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) are sensitive spectroscopy techniques that measure fluorescence intensity fluctuations of single molecules inside a femtoliter confocal volume. Both techniques are suitable for studying the formation of protein corona around NPs and for examining corona stability in situ in biological matrixes. In this review we provide a short description of FCS/FCCS and their application in PC studies, highlighting results from our work about the impact of surface chemistry of NPs on corona formation and NP intracellular fate.

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Prediction of the size of electroformed giant unilamellar vesicle using response surface methodology

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Salah Eddine Ghellab, Wei Mu, Qingchuang Li, Xiaojun Han

Abstract

The production of giant unilamellar vesicles (GUVs) with specific size and structure has been a challenge on the design of quantitative biological assays in cell-mimetic micro-compartments. In this study, the effect of electroformation parameters (electric potential, frequency, and temperature) on the size of GUVs was investigated. Using response surface methodology based on Box-Behnken design, GUVs from neutral, positive and negative charges were formulated. The average diameter of GUVs was determined for each formulation. The acquired data of these GUVs were successfully fitted with quadratic regression models. These models were applied to visualize the parameters for ideal GUVs with wanted diameters by the obtained phase diagrams. These results show that response surface methodology can be used to estimate the electroformation parameters for specifically sized GUVs.

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A chemical kinetic model for Ca<sup>2+</sup> induced spontaneous oscillatory contraction of myocardium

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Tala, W. Sun, J.P. Zhang, X.Y. Zhao, W.S. Guo

Abstract

The Ca2+ induced Spontaneous Oscillatory Contraction (Ca-SPOC) of cardiac myofibrils oscillate with a period similar to resting heartbeat of several animal species, and its auto-oscillatory properties set the basic rhythm of cardiac contraction. To explain the dynamics of Ca-SPOC, the present paper constructs a novel chemical kinetical model based upon the cooperative behavior between the two heads of myosin II dimer, also considering the reaction-diffusion effect of ATP inside myocardial fibers. The simulation results show that the concentration of ATP inside myocardial fibers oscillates over time under some special conditions, together with the proportions of myosin II dimers in different states periodically changing with time, which contributes to produce the sustained oscillations of contractive tension. These results indicate that the SPOC of muscles may be partly due to chemical oscillation involved in the actomyosin ATPase cycle, which has been ignored by the previous theoretical studies.

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Binding of quinazolinones to c-KIT G-quadruplex; an interplay between hydrogen bonding and π-π stacking

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Kiana Gholamjani Moghaddam, Alex H. de Vries, Siewert J. Marrink, Shirin Faraji

Abstract

Stabilization of G-quadruplex structures in the c-KIT promoter with the aid of ligands has become an area of great interest in potential cancer therapeutics. Understanding the binding process between ligands and G-quadruplex is essential for a discovery of selective ligands with high binding affinity to G-quadruplex. In the present work, binding mechanisms of 4-quinazolinones to c-KIT G-quadruplex were investigated theoretically by means of molecular dynamics (MD) simulations. To explore the binding affinity of ligands, binding free energy calculations were performed using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. We demonstrate that the key interactions in G-quadruplex-ligand complexes are π-π stacking and hydrogen bond interactions. However, neither of these two interactions alone determines the stability of the G-quadruplex-ligand complexes; rather, it is the result of an intricate interplay between the two. To further examine the nature of the binding, a free energy decomposition analysis at residue level was carried out. The results clearly demonstrate the crucial roles of two hot spot residues (DG4 and DG8) for the binding of ligands to c-KIT G-quadruplex, and highlight the importance of the planar aromatic moiety of ligands in G-quadruplex stabilization via π-π stacking interactions. Our study can assist in the design of new derivatives of 4-quinazolinone with high binding affinity for c-KIT G-quadruplex.

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Aggregation kinetics of short peptides: All-atom and coarse-grained molecular dynamics study

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Beata Szała, Andrzej Molski

Abstract

Peptides can aggregate into ordered structures with different morphologies. The aggregation mechanism and evolving structures are the subject of intense research. In this paper we have used molecular dynamics to examine the sequence-dependence of aggregation kinetics for three short peptides: octaalanine (Ala8), octaasparagine (Asn8), and the heptapeptide GNNQQNY (abbreviated as GNN). First, we compared the aggregation of 20 randomly distributed peptides using the coarse-grained MARTINI force field and the atomistic OPLS-AA force field. We found that the MARTINI and OPLS-AA aggregation kinetics are similar for Ala8, Asn8, and GNN. Second, we used the MARTINI force field to study the early stages of aggregation kinetics for a larger system with 72 peptides. In the initial stage of aggregation small clusters grow by monomer addition. In the second stage, when the free monomers are depleted, the dominant cluster growth path is cluster-cluster coalescence. We quantified the aggregation kinetics in terms of rate equations. Our study shows that the initial aggregation kinetics are similar for Ala8, Asn8, and GNN but the molecular details can be different, especially for MARTINI Ala8. We hypothesize that peptide aggregation proceed in two steps. In the first step amorphous aggregates are formed, and then, in the second step, they reorganize into ordered structures. We conclude that sequence-specific differences show up in the second step of aggregation.

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Force dependence of unbinding rate of kinesin motor during its processive movement on microtubule

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Si-Kao Guo, Xiao-Xuan Shi, Peng-Ye Wang, Ping Xie

Abstract

Kinesin is a biological molecular motor that can move continuously on microtubule until it unbinds. Here, we studied computationally the force dependence of the unbinding rate of the motor. Our results showed that while the unbinding rate under the forward load has the expected characteristic of “slip bond”, with the unbinding rate increasing monotonically with the increase of the forward load, the unbinding rate under the backward load shows counterintuitive characteristic of “slip-catch-slip bond”: as the backward load increases, the unbinding rate increases exponentially firstly, then drops rapidly and then increases again. Our calculated data are in agreement with the available single-molecule data from different research groups. The mechanism of the slip-catch-slip bond was revealed.

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Does hydrated glycine act as solidification nucleus at multi-kilobar conditions?

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Serena R. Alfarano, Hendrik Vondracek, Federico Sebastiani, Fabio Novelli, Claudius Hoberg, Inga Kolling, Jean-Blaise Brubach, Pascale Roy, Gerhard Schwaab, Martina Havenith

Abstract

The investigation of aqueous solutions containing biomolecules as a function of thermodynamic parameters, such as the pressure, is crucial for understanding biological processes. Here we report the first low frequency spectra of 1.5 M aqueous glycine from ambient pressure up to 8 kbar, i.e. in the pressure range which is crucial for understanding biological processes under extreme conditions.

We observe a linear pressure dependent blue shift of the specific N-C-C-O open/close mode at ∼320 cm-1 indicating an increasing compression of the solvated glycine. In contrast, the characteristic peak of the hydrogen bond hydration water network centered, at ambient conditions, at ∼184 cm-1 non-linearly blue shifts with increasing pressure, as well, but with a slower rate than the intramolecular peak.

This indicates that the macroscopic liquid-solid phase transition observed above 8 kbar pressure is driven by hydrated glycine as solidification nucleus.

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Prototyping a memristive-based device to analyze neuronal excitability

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): L. Lunelli, C. Collini, A.M. Jimenez-Garduño, A. Roncador, G. Giusti, R. Verucchi, L. Pasquardini, S. Iannotta, P. Macchi, L. Lorenzelli, C. Pederzolli, C. Musio, C. Potrich

Abstract

Many efforts have been spent in the last decade for the development of nanoscale synaptic devices integrated into neuromorphic circuits, trying to emulate the behavior of natural synapses. The study of brain properties with the standard approaches based on biocompatible electrodes coupled to conventional electronics, however, presents strong limitations, which in turn could be overcame by the in-situ growth of neuronal networks coupled to memristive devices. To meet this challenging task, here two different chips were designed and fabricated for culturing neuronal cells and sensing their electrophysiological activity. The first chip was designed to be connected to an external memristor, while the second chip was coated with TiO2 films owning memristive properties. The biocompatibility of chips was preliminary analyzed by culturing the hybrid motor-neuron cell line NSC-34 and by measuring the electrical activity of cells interfacing the chip with a standard patch-clamp setup. Next, neurons were seeded on chips and their activity measured with the same setup. For both cell types total current and voltage responses were evoked and recorded with optimal results with no breakdowns. In addition, an external stimulation was applied to cells through chip electrodes, being effective and causing no damage or pitfalls to the cells. Finally, the whole bio-hybrid system, i.e. the chip interconnected with a commercial memristor, was tested with promising results. Spontaneous electrical activity of neurons grown on the chip was indeed present and this signal was collected and sent to the memristor, changing its state. Taken together, we demonstrated the ability of memristor to work with a synaptic/plastic response together with natural systems, opening the way for the further implementation of basic computing elements able to perform both storage and processing of data, as in natural neurons.


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Identifying DNase I hypersensitive sites using multi-features fusion and F-score features selection via Chou's 5-steps rule

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Yunyun Liang, Shengli Zhang

Abstract

DNase I hypersensitive sites (DHSs) are regarded as those regions of chromatin that are sensitive to cleavage by the DNase I enzyme. Identification of DNase I hypersensitive sites will provide useful insights for discovering DNA's functional elements from the non-coding sequences in the biomedical research. Because of the significance for DNase I hypersensitive sites, it is indispensable to develop an accurate, fast, robust, and high-throughput automated computational model. In this paper, we develop a model named iDHSs-MFF by combining multiple fusion features and F-score features selection approach. The multiple fusion features include three auto-correlation descriptors based on the dinucleotide property matrix and the trinucleotide property matrix (TPM), Pseudo-DPM and Pseudo-TPM. Evaluation by the jackknife cross-validation indicates that the selected features by F-score are effective in the identification of DNase I hypersensitive sites. Experimental results on two benchmark datasets demonstrate that the proposed model outperforms some highly related models. Systematic application of this computational approach will greatly facilitate the analysis of transcriptional regulatory elements. The datasets and Matlab source codes are freely available at: https://github.com/shengli0201/Datasets.

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Fluorescence imaging of biochemical relationship between ubiquitinated histone 2A and Polycomb complex protein BMI1

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Barbara Storti, Simone Civita, Paolo Faraci, Giorgia Maroni, Indira Krishnan, Elena Levantini, Ranieri Bizzarri

Abstract

Several in vitro experiments have highlighted that the Polycomb group protein BMI1 plays a pivotal role in determining the biological functions of the Polycomb Repressor Complex 1 (PRC1), including its E3-ligase activity towards the Lys119 of histone H2A to yield ubiquitinated uH2A. The role of BMI1 in the epigenetic activity of PRC1 is particularly relevant in several cancers, particularly Non-Small Cell Lung Cancer (NSCLC). In this study, using indirect immunofluorescence protocols implemented on a confocal microscopy apparatus, we investigated the relationship between BMI1 and uH2A at different resolutions, in cultured (A549) and clinical NSCLC tissues, at the single cell level. In both cases, we observed a linear dependence of uH2A concentration upon BMI1 expression at the single nucleus level, indicating that the association of BMI1 to PRC1, which is needed for E3-ligase activity, occurs linearly in the physiological BMI1 concentration range. Additionally, in the NSCLC cell line model, a minor pool of uH2A may exist in absence of concurrent BMI1 expression, indicating non-exclusive, although predominant, role of BMI1 in the amplification of the E3-ligase activity of PRC1. A pharmacological downregulator of BMI1, PTC-209, was also tested in this context. Finally, the absence of significant colocalization (as measured by the Pearson's coefficient) between BMI1 and uH2A submicron clusters hints to a dynamic model where PRC1 resides transiently at ubiquitination sites. Beside unveiling subtle functional relationships between BMI1 and uH2A, these results also validate the use of uH2A as downstream “reporter” for BMI1 activity at the nuclear level in NSCLC contexts.

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Molecular dynamics simulations of membrane properties affected by plasma ROS based on the GROMOS force field

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

Author(s): Yujia Hu, Tong Zhao, Liang Zou, Xiaolong Wang, Yuantao Zhang

Abstract

Cold atmospheric plasma (CAP) has attracted substantial attention in the field of medical disinfection because its main components, reactive oxygen species (ROS), have a strong destructive effect on various cell components. The cell membrane plays an important role in maintaining proper cellular function by blocking harmful substances such as ROS. In this paper, we used molecular dynamics simulations to study the behaviour of different ROS at the membrane-water interface. The results showed that the cell membrane presented a weak barrier to hydrophobic ROS (O2) but effectively prevented hydrophilic ROS (OH, HO2, H2O2) from entering the cell. The plasma treatment significantly enhanced the permeability of the cell membrane to HO2, while the energetic barrier to other types of ROS changed only slightly. O2 very likely stopped in the centre of the lipid bilayer when crossing the membrane and there attacked the unsaturated region of the phospholipid. Cholesterol was most likely oxidized by HO2, causing a condensing effect that destroyed the integrity and fluidity of the cell membrane. The study also found that large amounts of ROS decreased the thickness of the cell membrane, and the phospholipid arrangement became disordered.

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Editorial Board

Publication date: October 2019

Source: Biophysical Chemistry, Volume 253

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Molecular dynamics simulations of mechanical stress on oxidized membranes

Publication date: Available online 13 September 2019

Source: Biophysical Chemistry

Author(s): Maria C. Oliveira, Maksudbek Yusupov, Annemie Bogaerts, Rodrigo M. Cordeiro

Abstract

Biomembranes are under constant attack of free radicals that may lead to lipid oxidation in conditions of oxidative stress. The products generated during lipid oxidation are responsible for structural and dynamical changes which may jeopardize the membrane function. For instance, the local rearrangements of oxidized lipid molecules may induce membrane rupture. In this study, we investigated the effects of mechanical stress on oxidized phospholipid bilayers (PLBs). Model bilayers were stretched until pore formation (or poration) using non-equilibrium molecular dynamics simulations. We studied single-component homogeneous membranes composed of lipid oxidation products, as well as two-component heterogeneous membranes with coexisting native and oxidized domains. In homogeneous membranes, the oxidation products with —OH and —OOH groups reduced the areal strain required for pore formation, whereas the oxidation product with O group behaved similarly to the native membrane. In heterogeneous membranes composed of oxidized and non-oxidized domains, we tested the hypothesis according to which poration may be facilitated at the domain interface region. However, results were inconclusive due to their large statistical variance and sensitivity to simulation setup parameters. We pointed out important technical issues that need to be considered in future simulations of mechanically-induced poration of heterogeneous membranes. This research is of interest for photodynamic therapy and plasma medicine, because ruptured and intact plasma membranes are experimentally considered hallmarks of necrotic and apoptotic cell death.

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Response to the “Comments on ‘Statistical thermodynamics of casein aggregation: Effects of salts and water’ [Biophys Chem. 247 (2019) 34–42]”

Publication date: Available online 13 September 2019

Source: Biophysical Chemistry

Author(s): Kaja Harton, Seishi Shimizu


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Amyloid fibril formation in the presence of water structure-affecting solutes

Publication date: Available online 12 September 2019

Source: Biophysical Chemistry

Author(s): Jaroslaw Wawer, Emilia Kaczkowska, Jakub Karczewski, Marcin Olszewski, Danuta Augustin-Nowacka, Joanna Krakowiak

Abstract

The impact of the differently hydrated non-electrolytes (protein structure destabilizers) on the fibrillation of hen egg white lysozyme (HEWL) was investigated. Two isomeric urea derivatives i.e. butylurea (BU) and N,N,N′,N′-tetramethylurea (TMU) were chosen as a tested compounds. The obtained results show that butylurea exerts greater impact on HEWL and its fibrillation than tetramethylurea. Both substances decrease the time of induction of the fibrillation (lag time) but only BU increases the efficiency of amyloidogenesis. For the systems with equivalent reduction of the HEWL stability (250 mM BU and 500 mM TMU) the not-equivalent increase of the protein fibrillation was recorded (higher for BU). This fact suggests that specific interactions with protein, possibly water mediated, are responsible for the action of the tested substances.

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Investigation of the binding between olfactory receptors and odorant molecules in <em>C.elegans</em> organism

Publication date: Available online 11 September 2019

Source: Biophysical Chemistry

Author(s): Edoardo Milanetti, Giorgio Gosti, Luca De Flaviis, Pier Paolo Olimpieri, Silvia Schwartz, Davide Caprini, Giancarlo Ruocco, Viola Folli

Abstract

The molecular mechanisms regulating the complex sensory system that underlies olfaction are still not completely understood. The compounds formed from the interaction of Olfactory Receptors (ORs) with volatile molecules play a crucial role in producing the sense of olfaction. Therefore, it is necessary to investigate the binding mechanisms between these receptors and small ligands. In this work, we focus our attention on C.elegans, this is a particularly suitable model organism because it is characterized by a nervous system composed of only 302 neurons. To study olfaction in C.elegans, we select 21 ORs from its olfactory neurons, and present a pipeline, consisting of several computational methods, with the aim of proposing a set of possible candidates for binding the selected C.elegans ORs. This pipeline introduces an approach based on the selection of templates, and threading, that takes advantage of the structural redundancy among membrane receptors. This procedure is widely replicable because it is based on algorithms that are publicly available and are freely hosted on institutional servers.

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Understanding membrane remodelling initiated by photosensitized lipid oxidation

Publication date: Available online 5 September 2019

Source: Biophysical Chemistry

Author(s): Tayana Mazin Tsubone, Mauricio S. Baptista, Rosangela Itri

Abstract

In this review, we describe how photooxidation changes membrane properties that can ultimately lead to permanent membrane damage. Lipid photooxidation occurs in the presence of reactive oxygen species such as singlet oxygen and by direct reactions of lipids with a photosensitizer in the excited state. Indeed, lipid oxidation triggers chemical transformations that can alter lipid packing; change the membrane surface area, thickness and elastic modulus; and induce pore formation and phase separation. Here, we highlight how lipid hydroperoxides promote membrane remodelling and phase separation. Further, we emphasize the alterations caused by truncated oxidized lipids that lead to increased membrane permeability. Finally, the consequences of lipid photooxidation on cell functions are also discussed.

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Pressure-dependent electronic structure calculations using integral equation-based solvation models

Publication date: Available online 27 August 2019

Source: Biophysical Chemistry

Author(s): Tim Pongratz, Patrick Kibies, Lukas Eberlein, Nicolas Tielker, Christoph Hölzl, Sho Imoto, Markus Beck Erlach, Simon Kurrmann, Paul Hendrik Schummel, Martin Hofmann, Oliver Reiser, Roland Winter, Werner Kremer, Hans Robert Kalbitzer, Dominik Marx, Dominik Horinek, Stefan M. Kast

Abstract

Recent methodological progress in quantum-chemical calculations using the “embedded cluster reference interaction site model” (EC-RISM) integral equation theory is reviewed in the context of applying it as a solvation model for calculating pressure-dependent thermodynamic and spectroscopic properties of molecules immersed in water. The methodology is based on self-consistent calculations of electronic and solvation structure around dissolved molecules where pressure enters the equations via an appropriately chosen solvent response function and the pure solvent density. Besides specification of a dispersion-repulsion force field for solute-solvent interactions, the EC-RISM approach derives the electrostatic interaction contributions directly from the wave function. We further develop and apply the method to a variety of benchmark cases for which computational or experimental reference data are either available in the literature or are generated specifically for this purpose in this work. Starting with an enhancement to predict hydration free energies at non-ambient pressures, which is the basis for pressure-dependent molecular population estimation, we demonstrate the performance on the calculation of the auto-ionization constant of water. Spectroscopic problems are addressed by studying the biologically relevant small osmolyte TMAO (trimethylamine N-oxide). Pressure-dependent NMR shifts are predicted and compared to experiments taking into account proper computational referencing methods that extend earlier work. The experimentally observed IR blue-shifts of certain vibrational bands of TMAO as well as of the cyanide anion are reproduced by novel methodology that allows for weighing equilibrium and non-equilibrium solvent relaxation effects. Taken together, the model systems investigated allow for an assessment of the reliability of the EC-RISM approach for studying pressure-dependent biophysical processes.

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Comment on “Statistical thermodynamics of casein aggregation: Effects of salts and water”, by Harton and Shimizu (Biophysical Chemistry, 247 (2019) 34–42)

Publication date: Available online 14 August 2019

Source: Biophysical Chemistry

Author(s): David S. Horne


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Category: Current Chemistry Research

Last update: 28.03.2018.






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