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European Biophysics Journal: EBJ

Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
Linda M Field, T G Emyr Davies, Andrias O O'Reilly, Martin S Williamson, B A Wallace
The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods...
January 9, 2017: European Biophysics Journal: EBJ
Manuela Maffei, Emanuela Longa, Antonio Sabatini, Alberto Vacca, Stefano Iotti
In vitro motility assay (IVMA) experiments were performed to analyze the movement of actin filaments sliding on a pavement of myosin molecules at different [ATP] and [ADP]. In standard experimental conditions at [ATP] = 2 mM, about 80% of the actin filaments move in unloaded conditions with a constant velocity. However, a fraction of at least 20% static actin filaments is always present. The accepted explanation is the occurrence of damaged "rigor"-like myosin heads that do not undergo the normal ATP-dependent cycling motion...
December 30, 2016: European Biophysics Journal: EBJ
Alfredo Sánchez-Solano, Angel A Islas, Thomas Scior, Bertin Paiz-Candia, Lourdes Millan-PerezPeña, Eduardo M Salinas-Stefanon
The mechanism of inactivation of mammalian voltage-gated Na(+) channels involves transient interactions between intracellular domains resulting in direct pore occlusion by the IFM motif and concomitant extracellular interactions with the β1 subunit. Navβ1 subunits constitute single-pass transmembrane proteins that form protein-protein associations with pore-forming α subunits to allosterically modulate the Na(+) influx into the cell during the action potential of every excitable cell in vertebrates. Here, we explored the role of the intracellular IFM motif of rNav1...
December 23, 2016: European Biophysics Journal: EBJ
Jian Tian, Chunlong Tu, Bobo Huang, Yitao Liang, Jian Zhou, Xuesong Ye
Electrophysiology and mechanics are two essential components in the functions of cardiomyocytes and skeletal muscle cells. The simultaneous recording of electrophysiological and mechanical activities is important for the understanding of mechanisms underlying cell functions. For example, on the one hand, mechanisms under cardiovascular drug effects will be investigated in a comprehensive way by the simultaneous recording of electrophysiological and mechanical activities. On the other hand, computational models of electromechanics provide a powerful tool for the research of cardiomyocytes...
December 23, 2016: European Biophysics Journal: EBJ
Vladimir P Zhdanov
The exocytotic pathway of secretion of molecules from cells includes transport by vesicles, tether-mediated fusion of vesicles with the plasma membrane accompanied by pore formation, and diffusion-mediated release of their contents via a pore to the outside. In related basic biophysical studies, vesicle-content release is tracked by measuring corresponding amperometric spikes. Although experiments of this type have a long history, the understanding of the underlying physics is still elusive. The present study elucidates the likely contribution of line energy, membrane tension and bending, osmotic pressure, hydration forces, and tethers to the potential energy for fusion-related pore formation and evolution...
December 10, 2016: European Biophysics Journal: EBJ
Giuseppina Simone
Phenotype variations define heterogeneity in biological and molecular systems, and play a crucial mechanistic role, and heterogeneity has been demonstrated in tumor cells. In this work, cells from blood of patients affected by colon cancer were analyzed and sorted using a microfluidic assay based on galactose-active moieties and incubated for culturing in severe combined immunodeficiency (SCID) mice. Based on the results of these experiments, a model based on Markov theory is implemented and discussed to explain the equilibrium existing between phenotypes of cell subpopulations sorted using the microfluidic assay...
December 9, 2016: European Biophysics Journal: EBJ
Muthukumaran Rajagopalan, Sangeetha Balasubramanian, Ilya Ioshikhes, Amutha Ramaswamy
Post translational modifications have a profound role in the regulation of several biological processes such as transcription, replication, and DNA repair. Acetylation and phosphorylation form a major class of post translational modifications involved in nucleosomal regulation by modifying its structure. The effect of post translational modifications on nucleosome structure could be better explored when the molecular trajectories explaining the time dependent structural evolution over a period of time is examined at the atomic level...
December 8, 2016: European Biophysics Journal: EBJ
Leila Karami, Ali Akbar Saboury, Elham Rezaee, Sayyed Abbas Tabatabai
The soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. Inhibition of sEH provides a new approach to the treatment of inflammation, hypertension and atherosclerosis. In this study, the binding modes and inhibition mechanisms of the new oxadiazole-based amide inhibitors of the human soluble epoxide hydrolase were investigated by molecular docking and molecular dynamics (MD) simulation followed by the MM-GBSA method to calculate the binding free energy of each inhibitor to sEH...
December 7, 2016: European Biophysics Journal: EBJ
Vratislav Cmiel, Josef Skopalik, Katerina Polakova, Jan Solar, Marketa Havrdova, David Milde, Ivan Justan, Massimiliano Magro, Zenon Starcuk, Ivo Provaznik
In the last few years, magnetically labeled cells have been intensively explored, and non-invasive cell tracking and magnetic manipulation methods have been tested in preclinical studies focused on cell transplantation. For clinical applications, it is desirable to know the intracellular pathway of nanoparticles, which can predict their biocompatibility with cells and the long-term imaging properties of labeled cells. Here, we quantified labeling efficiency, localization, and fluorescence properties of Rhodamine derivatized superparamagnetic maghemite nanoparticles (SAMN-R) in mesenchymal stromal cells (MSC)...
November 26, 2016: European Biophysics Journal: EBJ
Zhuoyang Lu, Hua Li, Chen Hou, Yunhua Peng, Jiangang Long, Jiankang Liu
Amyloid-β (Aβ) is widely recognized as toxic to neuronal cells. Its deposition on plasma and intracellular membranes and aggregation into amyloid plaques can disturb the composition and physiological function of neurons. Whether a physical property of cells, such as stiffness, is altered by endogenously overexpressed Aβ has not yet been investigated. In this study, we used human neuroblastoma cells stably overexpressing amyloid precursor protein (APP) and its Swedish mutant form (APPswe) to measure the changes in cell stiffness...
November 16, 2016: European Biophysics Journal: EBJ
O Dunne, M Weidenhaupt, P Callow, A Martel, M Moulin, S J Perkins, M Haertlein, V T Forsyth
Small-angle neutron scattering (SANS) is a powerful technique for the characterisation of macromolecular structures and interactions. Its main advantage over other solution state approaches is the ability to use D2O/H2O solvent contrast variation to selectively match out specific parts of a multi-component system. While proteins, nucleic acids, and lipids are readily distinguished in this way, it is not possible to locate different parts of a protein-protein system without the introduction of additional contrast by selective deuteration...
November 14, 2016: European Biophysics Journal: EBJ
Patrizia Iavicoli, François Rossi, Baptiste Lamarre, Angelo Bella, Maxim G Ryadnov, Luigi Calzolai
Peptide-lipid interactions support a variety of biological functions. Of particular interest are those that underpin fundamental mechanisms of innate immunity that are programmed in host defense or antimicrobial peptide sequences found virtually in all multicellular organisms. Here we synthetically modulate antimicrobial peptide-lipid interactions using an archetypal helical antimicrobial peptide and synthetic membranes mimicking bacterial and mammalian membranes in solution. We probe these interactions as a function of membrane-induced folding, membrane stability and peptide-lipid ratios using a correlative approach encompassing light scattering and spectroscopy measurements such as circular dichroism spectroscopy, fluorescence and nuclear magnetic resonance spectroscopy...
November 10, 2016: European Biophysics Journal: EBJ
Anatoliy I Dragan, Christopher M Read, Colyn Crane-Robinson
Structural modifications to interacting systems frequently lead to changes in both the enthalpy (heat) and entropy of the process that compensate each other, so that the Gibbs free energy is little changed: a major barrier to the development of lead compounds in drug discovery. The conventional explanation for such enthalpy-entropy compensation (EEC) is that tighter contacts lead to a more negative enthalpy but increased molecular constraints, i.e., a compensating conformational entropy reduction. Changes in solvation can also contribute to EEC but this contribution is infrequently discussed...
October 28, 2016: European Biophysics Journal: EBJ
Wallance Moreira Pazin, Danilo da Silva Olivier, Neus Vilanova, Ana Paula Ramos, Ilja Karina Voets, Ademilson Espencer Egea Soares, Amando Siuiti Ito
Green propolis, a mixture of beeswax and resinous compounds processed by Apis mellifera, displays several pharmacological properties. Artepillin C, the major compound in green propolis, consists of two prenylated groups bound to a phenyl group. Several studies have focused on the therapeutic effects of Artepillin C, but there is no evidence that it interacts with amphiphilic aggregates to mimic cell membranes. We have experimentally and computationally examined the interaction between Artepillin C and model membranes composed of dimyristoylphosphatidylcholine (DMPC) because phosphatidylcholine (PC) is one of the most abundant phospholipids in eukaryotic cell membranes...
October 26, 2016: European Biophysics Journal: EBJ
Juan J Dominguez Pardo, Jonas M Dörr, Aditya Iyer, Ruud C Cox, Stefan Scheidelaar, Martijn C Koorengevel, Vinod Subramaniam, J Antoinette Killian
A promising tool in membrane research is the use of the styrene-maleic acid (SMA) copolymer to solubilize membranes in the form of nanodiscs. Since membranes are heterogeneous in composition, it is important to know whether SMA thereby has a preference for solubilization of either specific types of lipids or specific bilayer phases. Here, we investigated this by performing partial solubilization of model membranes and analyzing the lipid composition of the solubilized fraction. We found that SMA displays no significant lipid preference in homogeneous binary lipid mixtures in the fluid phase, even when using lipids that by themselves show very different solubilization kinetics...
January 2017: European Biophysics Journal: EBJ
Beatrix Peter, Szilvia Bosze, Robert Horvath
Herbs and traditional medicines have been applied for thousands of years, but researchers started to study their mode of action at the molecular, cellular and tissue levels only recently. Nowadays, just like in ancient times, natural compounds are still determining factors in remedies. To support this statement, the recently won Nobel Prize for an anti-malaria agent from the plant sweet wormwood, which had been used to effectively treat the disease, could be mentioned. Among natural compounds and traditional Chinese medicines, the green tea polyphenol epigallocatechin gallate (EGCg) is one of the most studied active substances...
January 2017: European Biophysics Journal: EBJ
Jun Liu, Sven Falke, Bjoern Drobot, Dominik Oberthuer, Alexey Kikhney, Tobias Guenther, Karim Fahmy, Dmitri Svergun, Christian Betzel, Johannes Raff
The formation of stable and functional surface layers (S-layers) via self-assembly of surface-layer proteins on the cell surface is a dynamic and complex process. S-layers facilitate a number of important biological functions, e.g., providing protection and mediating selective exchange of molecules and thereby functioning as molecular sieves. Furthermore, S-layers selectively bind several metal ions including uranium, palladium, gold, and europium, some of them with high affinity. Most current research on surface layers focuses on investigating crystalline arrays of protein subunits in Archaea and bacteria...
January 2017: European Biophysics Journal: EBJ
Dominic Narang, Anubhuti Singh, Samrat Mukhopadhyay
Amyloid fibril formation by human β2-microglobulin (β2m) is associated with dialysis-related amyloidosis. In order to understand the mechanism of protein misfolding, it is important to characterize the nature and properties of various intermediates formed during protein unfolding. In this work, we studied the effect of pH change on the unfolding of β2m using a range of spectroscopic readouts. In order to investigate the local structural changes, we created single tryptophan (W60 and W95) mutants of β2m...
January 2017: European Biophysics Journal: EBJ
Peter Hugo Nelson
A solute-blocking model is presented that provides a kinetic explanation of osmosis and ideal solution thermodynamics. It validates a diffusive model of osmosis that is distinct from the traditional convective flow model of osmosis. Osmotic equilibrium occurs when the fraction of water molecules in solution matches the fraction of pure water molecules that have enough energy to overcome the pressure difference. Solute-blocking also provides a kinetic explanation for why Raoult's law and the other colligative properties depend on the mole fraction (but not the size) of the solute particles, resulting in a novel kinetic explanation for the entropy of mixing and chemical potential of ideal solutions...
January 2017: European Biophysics Journal: EBJ
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