23,464 results match your criteria Biophysical journal[Journal]


Electrophoretic Mobility of DNA in Solutions of High Ionic Strength.

Biophys J 2020 Apr 30. Epub 2020 Apr 30.

Department of Biochemistry, University of Iowa, Iowa City, Iowa. Electronic address:

The free-solution mobilities of small single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) have been measured by capillary electrophoresis in solutions containing 0.01-1.0 M sodium acetate. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.02.034DOI Listing

Exploration of Insulin Amyloid Polymorphism Using Raman Spectroscopy and Imaging.

Biophys J 2020 May 4. Epub 2020 May 4.

Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.

We aimed to investigate insulin amyloid fibril polymorphism caused by salt effects and heating temperature and to visualize the structural differences of the polymorphisms in situ using Raman imaging without labeling. The time course monitoring for amyloid formation was carried out in an acidic condition without any salts and with two species of salts (NaCl and NaSO) by heating at 60, 70, 80, and 90°C. The intensity ratio of two Raman bands at 1672 and 1657 cm due to antiparallel β-sheet and α-helix structures, respectively, was revealed to be an indicator of amyloid fibril formation, and the relative proportion of the β-sheet structure was higher in the case with salts, especially at a higher temperature with NaSO. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.031DOI Listing

Protein-Folding Analysis Using Features Obtained by Persistent Homology.

Biophys J 2020 May 5. Epub 2020 May 5.

WPI-ASHBi, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan; Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan.

Understanding the protein-folding process is an outstanding issue in biophysics; recent developments in molecular dynamics simulation have provided insights into this phenomenon. However, the large freedom of atomic motion hinders the understanding of this process. In this study, we applied persistent homology, an emerging method to analyze topological features in a data set, to reveal protein-folding dynamics. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.032DOI Listing

Tuning Cell Motility via Cell Tension with a Mechanochemical Cell Migration Model.

Biophys J 2020 May 4. Epub 2020 May 4.

Center for Quantitative Biology, Peking University, Beijing, China; Beijing International Center for Mathematical Research, Peking University, Beijing, China. Electronic address:

Cell migration is orchestrated by a complicated mechanochemical system. However, few cell migration models take into account the coupling between the biochemical network and mechanical factors. Here, we construct a mechanochemical cell migration model to study the cell tension effect on cell migration. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.030DOI Listing
May 2020
3.972 Impact Factor

AimB Is a Small Protein Regulator of Cell Size and MreB Assembly.

Biophys J 2020 May 4. Epub 2020 May 4.

Department of Biology, Rutgers University-Camden, Camden, New Jersey; Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, New Jersey. Electronic address:

The MreB actin-like cytoskeleton assembles into dynamic polymers that coordinate cell shape in many bacteria. In contrast to most other cytoskeleton systems, few MreB-interacting proteins have been well characterized. Here, we identify a small protein from Caulobacter crescentus, an assembly inhibitor of MreB (AimB). Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.029DOI Listing

Multiscale Coarse-Grained Approach to Investigate Self-Association of Antibodies.

Biophys J 2020 Apr 29. Epub 2020 Apr 29.

Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California. Electronic address:

Self-association of therapeutic monoclonal antibodies (mabs) are thought to modulate the undesirably high viscosity observed in their concentrated solutions. Computational prediction of such a self-association behavior is advantageous early during mab drug candidate selection when material availability is limited. Here, we present a coarse-grained (CG) simulation method that enables microsecond molecular dynamics simulations of full-length antibodies at high concentrations. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.022DOI Listing

Effects of Single Mutations on Protein Stability Are Gaussian Distributed.

Biophys J 2020 May 1. Epub 2020 May 1.

Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts. Electronic address:

The distribution of protein stability effects is known to be well approximated by a Gaussian distribution from previous empirical fits. Starting from first-principles statistical mechanics, we more rigorously motivate this empirical observation by deriving per-residue-position protein stability effects to be Gaussian. Our derivation requires the number of amino acids to be large, which is satisfied by the standard set of 20 amino acids found in nature. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.027DOI Listing

Structural and Hydrodynamic Characterization of Dimeric Human Oligoadenylate Synthetase 2.

Biophys J 2020 May 1. Epub 2020 May 1.

Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

Oligoadenylate synthetases (OASs) are a family of interferon-inducible enzymes that require double-stranded RNA (dsRNA) as a cofactor. Upon binding dsRNA, OAS undergoes a conformational change and is activated to polymerize ATP into 2'-5'-oligoadenylate chains. The OAS family consists of several isozymes, with unique domain organizations to potentially interact with dsRNA of variable length, providing diversity in viral RNA recognition. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.025DOI Listing

Microtubule Simulations Provide Insight into the Molecular Mechanism Underlying Dynamic Instability.

Biophys J 2020 May 1. Epub 2020 May 1.

Department of Chemistry, Chicago Center for Theoretical Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois. Electronic address:

The dynamic instability of microtubules (MTs), which refers to their ability to switch between polymerization and depolymerization states, is crucial for their function. It has been proposed that the growing MT ends are protected by a "GTP cap" that consists of GTP-bound tubulin dimers. When the speed of GTP hydrolysis is faster than dimer recruitment, the loss of this GTP cap will lead the MT to undergo rapid disassembly. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.028DOI Listing

Lattice Models for Protein Organization throughout Thylakoid Membrane Stacks.

Biophys J 2020 May 1. Epub 2020 May 1.

Department of Chemistry, University of California, Berkeley, California; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Lab, Berkeley, California. Electronic address:

Proteins in photosynthetic membranes can organize into patterned arrays that span the membrane's lateral size. Attractions between proteins in different layers of a membrane stack can play a key role in this ordering, as was suggested by microscopy and fluorescence spectroscopy and demonstrated by computer simulations of a coarse-grained model. The architecture of thylakoid membranes, however, also provides opportunities for interlayer interactions that instead disfavor the high protein densities of ordered arrangements. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.036DOI Listing

CompuCell3D Simulations Reproduce Mesenchymal Cell Migration on Flat Substrates.

Biophys J 2020 Apr 30. Epub 2020 Apr 30.

Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Instituto Nacional de Ciência e Tecnologia, Sistemas Complexos, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Program de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address:

Mesenchymal cell crawling is a critical process in normal development, in tissue function, and in many diseases. Quantitatively predictive numerical simulations of cell crawling thus have multiple scientific, medical, and technological applications. However, we still lack a low-computational-cost approach to simulate mesenchymal three-dimensional (3D) cell crawling. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.024DOI Listing

Membrane Association Transforms an Inert Anti-TCRβ Fab' Ligand into a Potent T Cell Receptor Agonist.

Biophys J 2020 Apr 23. Epub 2020 Apr 23.

Department of Chemistry, University of California, Berkeley, Berkeley, California. Electronic address:

The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.018DOI Listing

TENSCell: Imaging of Stretch-Activated Cells Reveals Divergent Nuclear Behavior and Tension.

Biophys J 2020 Apr 23. Epub 2020 Apr 23.

Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado. Electronic address:

Mechanisms of cellular and nuclear mechanosensation are unclear, partially because of a lack of methods that can reveal dynamic processes. Here, we present a new concept for a low-cost, three-dimensionally printed device that enables high-magnification imaging of cells during stretch. We observed that nuclei of mouse embryonic skin fibroblasts underwent rapid (within minutes) and divergent responses, characterized by nuclear area expansion during 5% strain but nuclear area shrinkage during 20% strain. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.035DOI Listing

Medin Oligomer Membrane Pore Formation: A Potential Mechanism of Vascular Dysfunction.

Biophys J 2020 May 1. Epub 2020 May 1.

Department of Biomedical Engineering, University of Arizona, Tucson, Arizona; Department of Medicine, University of Arizona, Tucson, Arizona. Electronic address:

Medin, a 50-amino-acid cleavage product of the milk fat globule-EGF factor 8 protein, is one of the most common forms of localized amyloid found in the vasculature of individuals older than 50 years. Medin induces endothelial dysfunction and vascular inflammation, yet despite its prevalence in the human aorta and multiple arterial beds, little is known about the nature of its pathology. Medin oligomers have been implicated in the pathology of aortic aneurysm, aortic dissection, and more recently, vascular dementia. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.026DOI Listing

Intercellular Sodium Regulates Repolarization in Cardiac Tissue with Sodium Channel Gain of Function.

Biophys J 2020 Apr 21. Epub 2020 Apr 21.

Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Polytechnic Institute and State University, Roanoke, Virginia; Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia. Electronic address:

In cardiac myocytes, action potentials are initiated by an influx of sodium (Na) ions via voltage-gated Na channels. Na channel gain of function (GOF), arising in both inherited conditions associated with mutation in the gene encoding the Na channel and acquired conditions associated with heart failure, ischemia, and atrial fibrillation, enhance Na influx, generating a late Na current that prolongs action potential duration (APD) and triggering proarrhythmic early afterdepolarizations (EADs). Recent studies have shown that Na channels are highly clustered at the myocyte intercalated disk, facilitating formation of Na nanodomains in the intercellular cleft between cells. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.014DOI Listing

Excitation Energy Migration Unveils Fuzzy Interfaces within the Amyloid Architecture.

Biophys J 2020 Apr 23. Epub 2020 Apr 23.

Centre for Protein Science, Design and Engineering, Mohali, Punjab, India; Department of Biological Sciences, Mohali, Punjab, India; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Punjab, India. Electronic address:

Amyloid fibrils are highly ordered nanoscopic protein aggregates comprising a cross-β amyloid core and are associated with deadly human diseases. Structural studies have revealed the supramolecular architecture of a variety of disease-associated amyloids. However, the critical role of transient intermolecular interactions between the disordered polypeptide segments of protofilaments in directing the supramolecular structure and nanoscale morphology remains elusive. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.015DOI Listing

Quantitative High-Resolution Imaging of Live Microbial Cells at High Hydrostatic Pressure.

Biophys J 2020 Apr 23. Epub 2020 Apr 23.

Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, New York. Electronic address:

The majority of the Earth's microbial biomass exists in the deep biosphere, in the deep ocean, and within the Earth's crust. Although other physical parameters in these environments, such as temperature or pH, can differ substantially, they are all under high pressures. Beyond emerging genomic information, little is known about the molecular mechanisms underlying the ability of these organisms to survive and grow at pressures that can reach over 1000-fold the pressure on the Earth's surface. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.017DOI Listing

Structural Analysis of Nonapeptides Derived from Elastin.

Biophys J 2020 Apr 25. Epub 2020 Apr 25.

UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Reims, France; Multiscale Molecular Modeling Platform, Université de Reims Champagne Ardenne, Reims, France. Electronic address:

Elastin-derived peptides are released from the extracellular matrix remodeling by numerous proteases and seem to regulate many biological processes, notably cancer progression. The canonical elastin peptide is VGVAPG, which harbors the XGXXPG consensus pattern, allowing interaction with the elastin receptor complex located at the surface of cells. Besides these elastokines, another class of peptides has been identified. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.019DOI Listing

Control of Platelet CLEC-2-Mediated Activation by Receptor Clustering and Tyrosine Kinase Signaling.

Biophys J 2020 Apr 29. Epub 2020 Apr 29.

Center for Theoretical Problems of Physico-chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Dmitry Rogachev National Medical Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Faculty of Physics, Lomonosov Moscow State University, Moscow, Russia; Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address:

Platelets are blood cells responsible for vascular integrity preservation. The activation of platelet receptor C-type lectin-like receptor II-type (CLEC-2) could partially mediate the latter function. Although this receptor is considered to be of importance for hemostasis, the rate-limiting steps of CLEC-2-induced platelet activation are not clear. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.023DOI Listing
April 2020
3.972 Impact Factor

Spectroscopic Characterization of Halorhodopsin Reconstituted into Nanodisks Using Native Lipids.

Biophys J 2020 Apr 29. Epub 2020 Apr 29.

Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Japan; Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Japan. Electronic address:

We successfully reconstituted single Natronomonas pharaonis halorhodopsin (NpHR) trimers into a nanodisk (ND) using the native archaeal lipid (NL) and an artificial lipid having a zwitterionic headgroup, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Incorporation of single trimeric NpHR into NDs was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, size-exclusion chromatography, and visible circular dichroism spectroscopy. The Cl binding affinity of NpHR in NDs using NL (NL-ND NpHR) or POPC (POPC-ND NpHR) was examined by absorption spectroscopy, showing that the Cl-releasing affinities (K) of these ND-reconstituted NpHRs are more than 10 times higher than that obtained from native NpHR membrane fragments (MFs) harvested from a NpHR-overexpressing archaeal strain (MF NpHR). Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.021DOI Listing
April 2020
3.972 Impact Factor

Measurement of the Internal Frictional Drag of the Bacterial Flagellar Motor by Fluctuation Analysis.

Biophys J 2020 Apr 29. Epub 2020 Apr 29.

Hefei National Laboratory for Physical Sciences at the Microscale, Hefei, Anhui, China; Department of Physics, University of Science and Technology of China, Hefei, Anhui, China. Electronic address:

The bacterial flagellar motor generates the torque that drives the rotation of bacterial flagellar filaments. The torque it generates depends sensitively on the frictional viscous drag on the motor, which includes the frictional viscous drag on the filaments (external load) and the internal frictional viscous drag on the rotor (internal load). The internal load was roughly estimated previously by modeling it as a sphere of a radius of 20 nm rotating in a lipid of viscosity of 100 cp but was never measured experimentally. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.020DOI Listing

Computing 3D Chromatin Configurations from Contact Probability Maps by Inverse Brownian Dynamics.

Biophys J 2020 May 29;118(9):2193-2208. Epub 2020 Feb 29.

Department of Chemical Engineering, Monash University, Melbourne, Victoria, Australia. Electronic address:

The three-dimensional (3D) organization of chromatin, on the length scale of a few genes, is crucial in determining the functional state-accessibility and amount of gene expression-of the chromatin. Recent advances in chromosome conformation capture experiments provide partial information on the chromatin organization in a cell population, namely the contact count between any segment pairs, but not on the interaction strength that leads to these contact counts. However, given the contact matrix, determining the complete 3D organization of the whole chromatin polymer is an inverse problem. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203009PMC

An Active Biomechanical Model of Cell Adhesion Actuated by Intracellular Tensioning-Taxis.

Biophys J 2020 Apr 23. Epub 2020 Apr 23.

Department of Orthopedics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea. Electronic address:

Cell adhesion to the extracellular matrix (ECM) is highly active and plays a crucial role in various physiological functions. The active response of cells to physicochemical cues has been universally discovered in multiple microenvironments. However, the mechanisms to rule these active behaviors of cells are still poorly understood. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.016DOI Listing

Tumble Kinematics of Escherichia coli near a Solid Surface.

Biophys J 2020 May 5;118(10):2400-2410. Epub 2020 May 5.

Laboratoire de Physique, ENS de Lyon, CNRS, Université Lyon, Lyon, France.

Bacteria tumble periodically, following environmental cues. Whether they can tumble near a solid surface is a basic issue for the inception of infection or mineral biofouling. Observing freely swimming Escherichia coli near and parallel to a glass surface imaged at high magnification (×100) and high temporal resolution (500 Hz), we identified tumbles as events starting (or finishing, respectively) in abrupt deceleration (or reacceleration, respectively) of the body motion. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231893PMC

Dynamics of the Buckling Transition in Double-Stranded DNA and RNA.

Biophys J 2020 Apr 29;118(7):1690-1701. Epub 2020 Feb 29.

Physics of Complex Biosystems, Physics Department, Technical University of Munich, Garching, Germany. Electronic address:

DNA under torsional strain undergoes a buckling transition that is the fundamental step in plectoneme nucleation and supercoil dynamics, which are critical for the processing of genomic information. Despite its importance, quantitative models of the buckling transition, in particular to also explain the surprising two-orders-of-magnitude difference between the buckling times for RNA and DNA revealed by single-molecule tweezers experiments, are currently lacking. Additionally, little is known about the configurations of the DNA during the buckling transition because they are not directly observable experimentally. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.01.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136337PMC

Choice of Force Field for Proteins Containing Structured and Intrinsically Disordered Regions.

Biophys J 2020 Apr 29;118(7):1621-1633. Epub 2020 Feb 29.

Central European Institute of Technology, Masaryk University, Brno, Czech Republic. Electronic address:

Biomolecular force fields optimized for globular proteins fail to properly reproduce properties of intrinsically disordered proteins. In particular, parameters of the water model need to be modified to improve applicability of the force fields to both ordered and disordered proteins. Here, we compared performance of force fields recommended for intrinsically disordered proteins in molecular dynamics simulations of three proteins differing in the content of ordered and disordered regions (two proteins consisting of a well-structured domain and of a disordered region with and without a transient helical motif and one disordered protein containing a region of increased helical propensity). Read More

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http://dx.doi.org/10.1016/j.bpj.2020.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136338PMC

Processivity and Velocity for Motors Stepping on Periodic Tracks.

Biophys J 2020 Apr 25;118(7):1537-1551. Epub 2020 Feb 25.

Department of Chemistry, The University of Texas at Austin, Austin, Texas.

Processive molecular motors enable cargo transportation by assembling into dimers capable of taking several consecutive steps along a cytoskeletal filament. In the well-accepted hand-over-hand stepping mechanism, the trailing motor detaches from the track and binds the filament again in the leading position. This requires fuel consumption in the form of ATP hydrolysis and coordination of the catalytic cycles between the leading and the trailing heads. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.01.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136348PMC

The Selectivity Filter Is Involved in the U-Type Inactivation Process of Kv2.1 and Kv3.1 Channels.

Biophys J 2020 May 15;118(10):2612-2620. Epub 2020 Apr 15.

Laboratory for Molecular, Cellular and Network Excitability, University of Antwerp, Antwerp, Belgium. Electronic address:

Voltage-gated potassium (Kv) channels display several types of inactivation processes, including N-, C-, and U-types. C-type inactivation is attributed to a nonconductive conformation of the selectivity filter (SF). It has been proposed that the activation gate and the channel's SF are allosterically coupled because the conformational changes of the former affect the structure of the latter and vice versa. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231921PMC

Bond Type and Discretization of Nonmuscle Myosin II Are Critical for Simulated Contractile Dynamics.

Biophys J 2020 Apr 21. Epub 2020 Apr 21.

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:

Molecular motors drive cytoskeletal rearrangements to change cell shape. Myosins are the motors that move, cross-link, and modify the actin cytoskeleton. The primary force generator in contractile actomyosin networks is nonmuscle myosin II (NMMII), a molecular motor that assembles into ensembles that bind, slide, and cross-link actin filaments (F-actin). Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.033DOI Listing

Speed and Diffusion of Kinesin-2 Are Competing Limiting Factors in Flagellar Length-Control Model.

Biophys J 2020 Apr 22. Epub 2020 Apr 22.

Department of Biology, Texas A&M University, College Station, Texas. Electronic address:

Flagellar length control in Chlamydomonas is a tractable model system for studying the general question of organelle size regulation. We have previously proposed that the diffusive return of the kinesin motor that powers intraflagellar transport can play a key role in length regulation. Here, we explore how the motor speed and diffusion coefficient for the return of kinesin-2 affect flagellar growth kinetics. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.034DOI Listing

Calcium-Lipid Interactions Observed with Isotope-Edited Infrared Spectroscopy.

Biophys J 2020 Apr 21. Epub 2020 Apr 21.

Department of Chemistry, University of Texas at Austin, Austin, Texas. Electronic address:

Calcium ions bind to lipid membranes containing anionic lipids; however, characterizing the specific ion-lipid interactions in multicomponent membranes has remained challenging because it requires nonperturbative lipid-specific probes. Here, using a combination of isotope-edited infrared spectroscopy and molecular dynamics simulations, we characterize the effects of a physiologically relevant (2 mM) Ca concentration on zwitterionic phosphatidylcholine and anionic phosphatidylserine lipids in mixed lipid membranes. We show that Ca alters hydrogen bonding between water and lipid headgroups by forming a coordination complex involving the lipid headgroups and water. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.013DOI Listing

z-STED Imaging and Spectroscopy to Investigate Nanoscale Membrane Structure and Dynamics.

Biophys J 2020 May 16;118(10):2448-2457. Epub 2020 Apr 16.

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden. Electronic address:

Super-resolution stimulated emission depletion (STED) microcopy provides optical resolution beyond the diffraction limit. The resolution can be increased laterally (xy) or axially (z). Two-dimensional STED has been extensively used to elucidate the nanoscale membrane structure and dynamics via imaging or combined with spectroscopy techniques such as fluorescence correlation spectroscopy (FCS) and spectral imaging. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231928PMC

Prior-Apprised Unsupervised Learning of Subpixel Curvilinear Features in Low Signal/Noise Images.

Biophys J 2020 May 19;118(10):2458-2469. Epub 2020 Apr 19.

Department of Chemistry, Princeton University, Princeton, New Jersey. Electronic address:

Many biophysical problems involve molecular and nanoscale targets moving next to a curvilinear track, e.g., a cytosolic cargo transported by motor proteins moving along a microtubule. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231927PMC

β Cells Operate Collectively to Help Maintain Glucose Homeostasis.

Biophys J 2020 May 15;118(10):2588-2595. Epub 2020 Apr 15.

Tokyo Tech World Research Hub Initiative (WRHI), Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan.

Residing in the islets of Langerhans in the pancreas, β cells contribute to glucose homeostasis by managing the body's insulin supply. Although it has been acknowledged that healthy β cells engage in heavy cell-to-cell communication to perform their homeostatic function, the exact role and effects of such communication remain partly understood. We offer a novel, to our knowledge, perspective on the subject in the form of 1) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and 2) empirical data analysis that reveals a qualitative shift in the cross-correlation structure of measured signals below and above the threshold glucose concentration. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231924PMC

Quantitative Study of the Chiral Organization of the Phage Genome Induced by the Packaging Motor.

Biophys J 2020 May 14;118(9):2103-2116. Epub 2020 Apr 14.

Department of Microbiology and Molecular Genetics, University of California at Davis, Davis, California; Department of Mathematics, University of California at Davis, Davis, California. Electronic address:

Molecular motors that translocate DNA are ubiquitous in nature. During morphogenesis of double-stranded DNA bacteriophages, a molecular motor drives the viral genome inside a protein capsid. Several models have been proposed for the three-dimensional geometry of the packaged genome, but very little is known of the signature of the molecular packaging motor. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203069PMC

Electroosmosis Dominates Electrophoresis of Antibiotic Transport Across the Outer Membrane Porin F.

Biophys J 2020 Apr 19. Epub 2020 Apr 19.

Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany. Electronic address:

We report that the dynamics of antibiotic capture and transport across a voltage-biased OmpF nanopore is dominated by the electroosmotic flow rather than the electrophoretic force. By reconstituting an OmpF porin in an artificial lipid bilayer and applying an electric field across it, we are able to elucidate the permeation of molecules and their mechanism of transport. This field gives rise to an electrophoretic force acting directly on a charged substrate but also indirectly via coupling to all other mobile ions, causing an electroosmotic flow. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.011DOI Listing

Structural Description of the Nipah Virus Phosphoprotein and Its Interaction with STAT1.

Biophys J 2020 May 18;118(10):2470-2488. Epub 2020 Apr 18.

Institut de Biologie Structurale, University Grenoble Alpes, CEA, CNRS, Grenoble, France. Electronic address:

The structural characterization of modular proteins containing long intrinsically disordered regions intercalated with folded domains is complicated by their conformational diversity and flexibility and requires the integration of multiple experimental approaches. Nipah virus (NiV) phosphoprotein, an essential component of the viral RNA transcription/replication machine and a component of the viral arsenal that hijacks cellular components and counteracts host immune responses, is a prototypical model for such modular proteins. Curiously, the phosphoprotein of NiV is significantly longer than the corresponding protein of other paramyxoviruses. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231922PMC

Platelet Factor 4 Interactions with Short Heparin Oligomers: Implications for Folding and Assembly.

Biophys J 2020 Apr 21. Epub 2020 Apr 21.

Chemistry Department, University of Massachusetts-Amherst, Amherst, Massachusetts. Electronic address:

Association of platelet factor 4 (PF4) with heparin is a first step in formation of aggregates implicated in the development of heparin-induced thrombocytopenia (HIT), a potentially fatal immune disorder affecting 1-5% of patients receiving heparin. Despite being a critically important element in HIT etiology, relatively little is known about the specific molecular mechanism of PF4-heparin interactions. This work uses native mass spectrometry to investigate PF4 interactions with relatively short heparin chains (up to decasaccharides). Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.012DOI Listing
April 2020
3.972 Impact Factor

Rapid Quantification of Protein-Ligand Binding via F NMR Lineshape Analysis.

Biophys J 2020 May 15;118(10):2537-2548. Epub 2020 Apr 15.

Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina. Electronic address:

Fluorine incorporation is ideally suited to many NMR techniques, and incorporation of fluorine into proteins and fragment libraries for drug discovery has become increasingly common. Here, we use one-dimensional F NMR lineshape analysis to quantify the kinetics and equilibrium thermodynamics for the binding of a fluorine-labeled Src homology 3 (SH3) protein domain to four proline-rich peptides. SH3 domains are one of the largest and most well-characterized families of protein recognition domains and have a multitude of functions in eukaryotic cell signaling. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231920PMC

Small Conformational Changes Underlie Evolution of Resistance to NNRTI in HIV Reverse Transcriptase.

Biophys J 2020 May 16;118(10):2489-2501. Epub 2020 Apr 16.

Indian Institute of Science Education and Research Mohali, SAS Nagar, Punjab, India. Electronic address:

Despite achieving considerable success in reducing the number of fatalities due to acquired immunodeficiency syndrome, emergence of resistance against the reverse transcriptase (RT) inhibitor drugs remains one of the biggest challenges of the human immunodeficiency virus antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) form a large class of drugs and a crucial component of ART. In NNRTIs, even a single resistance mutation is known to make the drugs completely ineffective. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231925PMC
May 2020
3.972 Impact Factor

Supercritical Angle Fluorescence Microscopy and Spectroscopy.

Biophys J 2020 May 11;118(10):2339-2348. Epub 2020 Apr 11.

Saints-Pères Paris Institute for the Neurosciences, Université de Paris, CNRS, Paris, France; Chaire d'Excellence Junior, Université Sorbonne Paris Cité, Paris, France.

Fluorescence detection, either involving propagating or near-field emission, is widely being used in spectroscopy, sensing, and microscopy. Total internal reflection fluorescence (TIRF) confines fluorescence excitation by an evanescent (near) field, and it is a popular contrast generator for surface-selective fluorescence assays. Its emission equivalent, supercritical angle fluorescence (SAF), is comparably less established, although it achieves a similar optical sectioning as TIRF does. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231923PMC

Aggregation Temperature of Escherichia coli Depends on Steepness of the Thermal Gradient.

Biophys J 2020 Apr 19. Epub 2020 Apr 19.

Department of Physics, University of California, San Diego, La Jolla, California. Electronic address:

Bacterial chemotaxis, the directed migration of bacteria in a gradient of chemoattractant, is one of the most well-studied and well-understood processes in cell biology. On the other hand, bacterial thermotaxis, the directed migration of bacteria in a gradient of temperature, is understood relatively poorly, with somewhat conflicting reports by different groups. One of the reasons for that is the relative technical difficulty of the generation of well-defined gradients of temperature that are sufficiently steep to elicit readily detectable thermotaxis. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.02.033DOI Listing

Exon Definition Facilitates Reliable Control of Alternative Splicing in the RON Proto-Oncogene.

Biophys J 2020 Apr 3;118(8):2027-2041. Epub 2020 Mar 3.

Institute of Molecular Biology, Mainz, Germany. Electronic address:

Alternative splicing is a key step in eukaryotic gene expression that allows for the production of multiple transcript and protein isoforms from the same gene. Even though splicing is perturbed in many diseases, we currently lack insights into regulatory mechanisms promoting its precision and efficiency. We analyze high-throughput mutagenesis data obtained for an alternatively spliced exon in the proto-oncogene RON and determine the functional units that control this splicing event. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175406PMC

To Hop or not to Hop: Exceptions in the FCS Diffusion Law.

Biophys J 2020 May 15;118(10):2434-2447. Epub 2020 Apr 15.

Department of Biological Sciences and NUS Centre for Bio-Imaging Sciences, National University of Singapore, Singapore, Singapore; Department of Chemistry, National University of Singapore, Singapore, Singapore. Electronic address:

Diffusion obstacles in membranes have not been directly visualized because of fast membrane dynamics and the occurrence of subresolution molecular complexes. To understand the obstacle characteristics, mobility-based methods are often used as an indirect way of assessing the membrane structure. Molecular movement in biological plasma membranes is often characterized by anomalous diffusion, but the exact underlying mechanisms are still elusive. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231916PMC

A Mechanical Instability in Planar Epithelial Monolayers Leads to Cell Extrusion.

Biophys J 2020 May 11;118(10):2549-2560. Epub 2020 Apr 11.

Department of Biological Sciences, Osaka University, Machikaneyama-cho, Toyonaka, Japan.

In cell extrusion, a cell embedded in an epithelial monolayer loses its apical or basal surface and is subsequently squeezed out of the monolayer by neighboring cells. Cell extrusions occur during apoptosis, epithelial-mesenchymal transition, or precancerous cell invasion. They play important roles in embryogenesis, homeostasis, carcinogenesis, and many other biological processes. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231918PMC

Heating-Induced DMPC/Glycyrrhizin Bicelle-to-Vesicle Transition: A X-Ray Contrast Variation Study.

Biophys J 2020 May 8;118(10):2411-2425. Epub 2020 Apr 8.

Physical and Biophysical Chemistry, Bielefeld University, Bielefeld, Germany. Electronic address:

In this study, we investigated the conversion of lipid bicelles into vesicles in the case of a system composed of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the saponin glycyrrhizin in the presence of sucrose. Glycyrrhizin is a biosurfactant present in the licorice root and possesses a triterpenic hydrophobic backbone and a hydrophilic headgroup built from two sugar molecules. The aim of this study is to determine the initial bicelle size at temperatures below the lipid's main phase transition temperature T and, based on these results, characteristics of the temperature-induced bicelle-to-vesicle transition. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231895PMC

Predicting Protein Functional Motions: an Old Recipe with a New Twist.

Biophys J 2020 May 4;118(10):2513-2525. Epub 2020 Apr 4.

University Grenoble Alpes, CNRS, Inria, Grenoble INP, LJK, Grenoble, France.

Large macromolecules, including proteins and their complexes, very often adopt multiple conformations. Some of them can be seen experimentally, for example with x-ray crystallography or cryo-electron microscopy. This structural heterogeneity is not occasional and is frequently linked with specific biological function. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231898PMC

Reviving Protein-Observed F Lineshape Analysis for Deep Insight into Protein-Ligand Binding Events.

Biophys J 2020 May 21;118(10):2333-2335. Epub 2020 Apr 21.

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania; Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.bpj.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231914PMC

Spatiotemporal Dynamics of Dilute Red Blood Cell Suspensions in Low-Inertia Microchannel Flow.

Biophys J 2020 May 4;118(10):2561-2573. Epub 2020 Apr 4.

School of Engineering, Institute for Multiscale Thermofluids, University of Edinburgh, Edinburgh, United Kingdom. Electronic address:

Microfluidic technologies are commonly used for the manipulation of red blood cell (RBC) suspensions and analyses of flow-mediated biomechanics. To enhance the performance of microfluidic devices, understanding the dynamics of the suspensions processed within is crucial. We report novel, to our knowledge, aspects of the spatiotemporal dynamics of RBC suspensions flowing through a typical microchannel at low Reynolds number. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231897PMC

Chromatin Viscoelasticity Measured by Local Dynamic Analysis.

Biophys J 2020 May 14;118(9):2258-2267. Epub 2020 Apr 14.

Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan, Israel.

The nucleus in eukaryotic cells is a crowded environment that consists of genetic code along the DNA, together with a condensed solution of proteins, RNA, and other molecules. It is subjected to highly dynamic processes, including cell division, transcription, and DNA repair. In addition, the genome in the nucleus is subjected to external forces applied by the cytoplasmic skeleton and neighboring cells, as well as to internal nuclear forces. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203068PMC