22,829 results match your criteria Biophysical journal[Journal]


A Two-Pulse Cellular Stimulation Test Elucidates Variability and Mechanisms in Signaling Pathways.

Biophys J 2019 Jan 30. Epub 2019 Jan 30.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address:

Mammalian cells respond in a variable manner when provided with physiological pulses of ligand, such as low concentrations of acetylcholine present for just tens of seconds or TNFα for just tens of minutes. For a two-pulse stimulation, some cells respond to both pulses, some do not respond, and yet others respond to only one or the other pulse. Are these different response patterns the result of the small number of ligands being able to only stochastically activate the pathway at random times or an output pattern from a deterministic algorithm responding differently to different stimulation intervals? If the response is deterministic in nature, what parameters determine whether a response is generated or skipped? To answer these questions, we developed a two-pulse test that utilizes different rest periods between stimulation pulses. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.022DOI Listing
January 2019

Anomalous Diffusion in Inverted Variable-Lengthscale Fluorescence Correlation Spectroscopy.

Biophys J 2019 Jan 30. Epub 2019 Jan 30.

Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, Canada. Electronic address:

Using fluorescence correlation spectroscopy (FCS) to distinguish between different types of diffusion processes is often a perilous undertaking because the analysis of the resulting autocorrelation data is model dependant. Two recently introduced strategies, however, can help move toward a model-independent interpretation of FCS experiments: 1) the obtention of correlation data at different length scales and 2) their inversion to retrieve the mean-squared displacement associated with the process under study. We use computer simulations to examine the signature of several biologically relevant diffusion processes (simple diffusion, continuous-time random walk, caged diffusion, obstructed diffusion, two-state diffusion, and diffusing diffusivity) in variable-length-scale FCS. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.024DOI Listing
January 2019

CcdB at pH 4 Forms a Partially Unfolded State with a Dry Core.

Biophys J 2019 Feb 1. Epub 2019 Feb 1.

Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. Electronic address:

pH is an important factor that affects the protein structure, stability, and activity. Here, we probe the nature of the low-pH structural form of the homodimeric CcdB (controller of cell death B) protein. Characterization of CcdB protein at pH 4 and 300 K using circular dichroism spectroscopy, 8-anilino-1-naphthalene-sulphonate binding, and Trp solvation studies suggests that it forms a partially unfolded state with a dry core at equilibrium under these conditions. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.026DOI Listing
February 2019

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics.

Biophys J 2019 Jan 29. Epub 2019 Jan 29.

Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada. Electronic address:

Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.021DOI Listing
January 2019

A Cholesterol Analog Induces an Oligomeric Reorganization of VDAC.

Biophys J 2019 Feb 1. Epub 2019 Feb 1.

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

The oligomeric organization of the voltage-dependent anion-selective channel (VDAC) and its interactions with hexokinase play integral roles in mitochondrially mediated apoptotic signaling. Various small to large assemblies of VDAC are observed in mitochondrial outer membranes, but they do not predominate in detergent-solubilized VDAC samples. In this study, a cholesterol analog, cholesteryl-hemisuccinate (CHS), was shown to induce the formation of detergent-soluble VDAC multimers. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.031DOI Listing
February 2019

Lipid Unsaturation Properties Govern the Sensitivity of Membranes to Photoinduced Oxidative Stress.

Biophys J 2019 Feb 2. Epub 2019 Feb 2.

Sorbonne Université, Faculté des Sciences et Ingénierie, CNRS, Laboratoire Jean Perrin, Paris, France. Electronic address:

Unsaturated lipid oxidation is a fundamental process involved in different aspects of cellular bioenergetics; dysregulation of lipid oxidation is often associated with cell aging and death. To study how lipid oxidation affects membrane biophysics, we used a chlorin photosensitizer to oxidize vesicles of various lipid compositions and degrees of unsaturation in a controlled manner. We observed different shape transitions that can be interpreted as an increase in the area of the targeted membrane followed by a decrease. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.033DOI Listing
February 2019

High-Copy-Number Plasmid Segregation-Single-Molecule Dynamics in Single Cells.

Biophys J 2019 Jan 29. Epub 2019 Jan 29.

Department of Physics, National Taiwan Normal University, Taipei, Taiwan. Electronic address:

Bacterial high-copy-number (hcn) plasmids provide an excellent model to study the underlying physical mechanisms of DNA segment segregation in an intracellular context. Using two-color fluorescent repressor-operator systems and a synthetic repressible replication origin, we tracked the motion and segregation of single hcn plasmid molecules in individual cells. The plasmid diffusion dynamics revealed between-plasmid temporal associations (clustering) as well as entropic and elastic recoiling forces in the confined intracellular spaces outside of nucleoids. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.019DOI Listing
January 2019

Single-Channel Resolution of the Interaction between C-Terminal Ca1.3 Isoforms and Calmodulin.

Biophys J 2019 Feb 1. Epub 2019 Feb 1.

Center of Pharmacology, University of Cologne, Cologne, Germany; Cologne University of Applied Sciences, Cologne, Germany.

Voltage-dependent calcium (Ca) 1.3 channels are involved in the control of cellular excitability and pacemaking in neuronal, cardiac, and sensory cells. Various proteins interact with the alternatively spliced channel C-terminus regulating gating of Ca1. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.025DOI Listing
February 2019

The Effect of Cortical Elasticity and Active Tension on Cell Adhesion Mechanics.

Biophys J 2019 Jan 24. Epub 2019 Jan 24.

MeBioS, KU Leuven, Heverlee, Belgium.

We consider a cell as an elastic, contractile shell surrounding a liquid incompressible cytoplasm and with nonspecific adhesion. We perform numerical simulations of this model to study the mechanics of cell-cell separation. By variation of parameters, we are able to recover well-known limits of the Johnson-Kendall-Roberts theory, the Derjaguin-Muller-Toporov model, adhesive vesicles with surface tension (Brochard-Wyart and de Gennes derivation), and thin elastic shells. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.015DOI Listing
January 2019

How ARVC-Related Mutations Destabilize Desmoplakin: An MD Study.

Biophys J 2019 Jan 30. Epub 2019 Jan 30.

Interdisciplinary Center for Scientific Computing, Heidelberg University, Mathematikon, Heidelberg, Germany; Heidelberg Institute for Theoretical Studies, Heidelberg, Germany. Electronic address:

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial heart disease linked to mutations in several desmosomal proteins, but the specific effects of these mutations on the molecular level are poorly understood. Among the many documented ARVC-related genetic variants, a striking hotspot of nine mutations has been identified in the plakin domain of desmoplakin. This hotspot can be found at the meeting point of three different subdomains of desmoplakin: two spectrin repeats and a Src homology 3 domain. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.023DOI Listing
January 2019

Influenza Hemagglutinin Modulates Phosphatidylinositol 4,5-bisphosphate Membrane Clustering.

Biophys J 2019 Jan 25. Epub 2019 Jan 25.

Department of Physics and Astronomy, University of Maine, Orono, Maine. Electronic address:

The lipid phosphatidylinositol 4,5-bisphosphate (PIP2) forms nanoscopic clusters in cell plasma membranes; however, the processes determining PIP2 mobility and thus its spatial patterns are not fully understood. Using super-resolution imaging of living cells, we find that PIP2 is tightly colocalized with and modulated by overexpression of the influenza viral protein hemagglutinin (HA). Within and near clusters, HA and PIP2 follow a similar spatial dependence, which can be described by an HA-dependent potential gradient; PIP2 molecules move as if they are attracted to the center of clusters by a radial force of 0. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.017DOI Listing
January 2019

Structural Analysis of a Trimer of β-Microgloblin Fragment by Molecular Dynamics Simulations.

Biophys J 2019 Jan 23. Epub 2019 Jan 23.

Department of Physics, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan; Structural Biology Research Center, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan; Center for Computational Science, Graduate School of Engineering, Nagoya University, Nagoya, Aichi, Japan; Information Technology Center, Nagoya University, Nagoya, Aichi, Japan; JST-CREST, Nagoya, Aichi, Japan. Electronic address:

A peptide β-m, which is a fragment from residue 21 to residue 31 of β-microgloblin, is experimentally known to self-assemble and form amyloid fibrils. In order to understand the mechanism of amyloid fibril formations, we applied the replica-exchange molecular dynamics method to the system consisting of three fragments of β-m. From the analyses on the temperature dependence, we found that there is a clear phase transition temperature in which the peptides aggregate with each other. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.11.3143DOI Listing
January 2019

Gramicidin Increases Lipid Flip-Flop in Symmetric and Asymmetric Lipid Vesicles.

Biophys J 2019 Jan 25. Epub 2019 Jan 25.

Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.

Unlike most transmembrane proteins, phospholipids can migrate from one leaflet of the membrane to the other. Because this spontaneous lipid translocation (flip-flop) tends to be very slow, cells facilitate the process with enzymes that catalyze the transmembrane movement and thereby regulate the transbilayer lipid distribution. Nonenzymatic membrane-spanning proteins with unrelated primary functions have also been found to accelerate lipid flip-flop in a nonspecific manner and by various hypothesized mechanisms. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.016DOI Listing
January 2019

Cooperative Changes in Solvent Exposure Identify Cryptic Pockets, Switches, and Allosteric Coupling.

Biophys J 2019 Jan 25. Epub 2019 Jan 25.

Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri; Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, Missouri. Electronic address:

Proteins are dynamic molecules that undergo conformational changes to a broad spectrum of different excited states. Unfortunately, the small populations of these states make it difficult to determine their structures or functional implications. Computer simulations are an increasingly powerful means to identify and characterize functionally relevant excited states. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.11.3144DOI Listing
January 2019

Will the Real Cryptic Pocket Please Stand Out?

Authors:
Rommie E Amaro

Biophys J 2019 Jan 26. Epub 2019 Jan 26.

Department of Chemistry and Biochemistry, UC San Diego, La Jolla, California. Electronic address:

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http://dx.doi.org/10.1016/j.bpj.2019.01.018DOI Listing
January 2019

Type IV Pilin Post-Translational Modifications Modulate Material Properties of Bacterial Colonies.

Biophys J 2019 Jan 29. Epub 2019 Jan 29.

Institute for Biological Physics, University of Cologne, Cologne, Germany. Electronic address:

Bacterial type 4 pili (T4P) are extracellular polymers that initiate the formation of microcolonies and biofilms. T4P continuously elongate and retract. These pilus dynamics crucially affect the local order, shape, and fluidity of microcolonies. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.020DOI Listing
January 2019

The Investigation of Protein Diffusion via H-Cell Microfluidics.

Biophys J 2019 Feb 22;116(4):595-609. Epub 2019 Jan 22.

Department of Biotechnology, Delft University of Technology, Delft, the Netherlands.

In this study, we developed a microfluidics method, using a so-called H-cell microfluidics device, for the determination of protein diffusion coefficients at different concentrations, pHs, ionic strengths, and solvent viscosities. Protein transfer takes place in the H-cell channels between two laminarly flowing streams with each containing a different initial protein concentration. The protein diffusion coefficients are calculated based on the measured protein mass transfer, the channel dimensions, and the contact time between the two streams. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.014DOI Listing
February 2019

Equilibrium Modeling of the Mechanics and Structure of the Cancer Glycocalyx.

Biophys J 2019 Feb 15;116(4):694-708. Epub 2019 Jan 15.

Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York. Electronic address:

The glycocalyx is a thick coat of proteins and carbohydrates on the outer surface of all eukaryotic cells. Overproduction of large, flexible or rod-like biopolymers, including hyaluronic acid and mucins, in the glycocalyx strongly correlates with the aggression of many cancer types. However, theoretical frameworks to predict the effects of these changes on cancer cell adhesion and other biophysical processes remain limited. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00063495193003
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http://dx.doi.org/10.1016/j.bpj.2018.12.023DOI Listing
February 2019
2 Reads

Non-sinusoidal Waveform in Temperature-Compensated Circadian Oscillations.

Biophys J 2019 Feb 15;116(4):741-751. Epub 2019 Jan 15.

Interdisciplinary Theoretical and Mathematical Sciences Program, RIKEN, Wako, Japan; Theoretical Biology Laboratory, RIKEN, Wako, Japan.

Time series of biological rhythms are of various shapes. Here, we investigated the waveforms of circadian rhythms in gene-protein dynamics using a newly developed, to our knowledge, index to quantify the degree of distortion from a sinusoidal waveform. In general, most biochemical reactions accelerate with increasing temperature, but the period of circadian rhythms remains relatively stable with temperature change, a phenomenon known as "temperature compensation. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.022DOI Listing
February 2019

The Phospholamban Pentamer Alters Function of the Sarcoplasmic Reticulum Calcium Pump SERCA.

Biophys J 2019 Feb 22;116(4):633-647. Epub 2019 Jan 22.

Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

The interaction of phospholamban (PLN) with the sarco-endoplasmic reticulum Ca-ATPase (SERCA) pump is a major regulatory axis in cardiac muscle contractility. The prevailing model involves reversible inhibition of SERCA by monomeric PLN and storage of PLN as an inactive pentamer. However, this paradigm has been challenged by studies demonstrating that PLN remains associated with SERCA and that the PLN pentamer is required for the regulation of cardiac contractility. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.013DOI Listing
February 2019
1 Read

Durotaxis by Human Cancer Cells.

Biophys J 2019 Feb 12;116(4):670-683. Epub 2019 Jan 12.

Cell Biology Section, Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland. Electronic address:

Durotaxis is a type of directed cell migration in which cells respond to a gradient of extracellular stiffness. Using automated tracking of positional data for large sample sizes of single migrating cells, we investigated 1) whether cancer cells can undergo durotaxis; 2) whether cell durotactic efficiency varies depending on the regional compliance of stiffness gradients; 3) whether a specific cell migration parameter such as speed or time of migration correlates with durotaxis; and 4) whether Arp2/3, previously implicated in leading edge dynamics and migration, contributes to cancer cell durotaxis. Although durotaxis has been characterized primarily in nonmalignant mesenchymal cells, little is known about its role in cancer cell migration. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00063495193002
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http://dx.doi.org/10.1016/j.bpj.2019.01.009DOI Listing
February 2019
2 Reads

Lipid-Conjugated Rigidochromic Probe Discloses Membrane Alteration in Model Cells of Krabbe Disease.

Biophys J 2019 Feb 25;116(3):477-486. Epub 2018 Dec 25.

NEST, Scuola Normale Superiore and Istituto Nanoscienze CNR (NANO-CNR), Piazza San Silvestro, Pisa, Italy; Department of Chemistry and CSGI, University of Florence, Florence, Italy. Electronic address:

The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (L or lipid raft) and more disordered (L) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the L and L domains in living cells on account of its large fluorescence lifetime variation in the two phases. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.11.3141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369402PMC
February 2019

Decoding Calcium Signaling Dynamics during Drosophila Wing Disc Development.

Biophys J 2019 Feb 11;116(4):725-740. Epub 2019 Jan 11.

Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana. Electronic address:

The robust specification of organ development depends on coordinated cell-cell communication. This process requires signal integration among multiple pathways, relying on second messengers such as calcium ions. Calcium signaling encodes a significant portion of the cellular state by regulating transcription factors, enzymes, and cytoskeletal proteins. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.007DOI Listing
February 2019

Fold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs.

Biophys J 2019 Feb 12;116(4):709-724. Epub 2019 Jan 12.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut; Department of Biomedical Engineering, Yale University, New Haven, Connecticut. Electronic address:

The transcription factor nuclear factor (NF)-κB promotes inflammatory and stress-responsive gene transcription across a range of cell types in response to the cytokine tumor necrosis factor (TNF). Although NF-κB signaling exhibits significant variability across single cells, some target genes supporting high levels of TNF-inducible transcription exhibit fold-change detection of NF-κB, which may buffer against stochastic variation in signaling molecules. It is unknown whether fold-change detection is maintained at NF-κB target genes with low levels of TNF-inducible transcription, for which stochastic promoter events may be more pronounced. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.011DOI Listing
February 2019

A Dynamic Hydrophobic Core and Surface Salt Bridges Thermostabilize a Designed Three-Helix Bundle.

Biophys J 2019 Feb 12;116(4):621-632. Epub 2019 Jan 12.

Department of Biology, Santa Clara University, Santa Clara, California. Electronic address:

Thermostable proteins are advantageous in industrial applications, as pharmaceuticals or biosensors, and as templates for directed evolution. As protein-design methodologies improve, bioengineers are able to design proteins to perform a desired function. Although many rationally designed proteins end up being thermostable, how to intentionally design de novo, thermostable proteins is less clear. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.012DOI Listing
February 2019
1 Read

Identification of Binding Sites for Efflux Pump Inhibitors of the AcrAB-TolC Component AcrA.

Biophys J 2019 Feb 12;116(4):648-658. Epub 2019 Jan 12.

Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma. Electronic address:

The overexpression of multidrug efflux pumps is an important mechanism of clinical resistance in Gram-negative bacteria. Recently, four small molecules were discovered that inhibit efflux in Escherichia coli and interact with the AcrAB-TolC efflux pump component AcrA. However, the binding site(s) for these molecules was not determined. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.010DOI Listing
February 2019

Core-Shell Modeling of Light Scattering by Vesicles: Effect of Size, Contents, and Lamellarity.

Biophys J 2019 Feb 10;116(4):659-669. Epub 2019 Jan 10.

Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Having a fast, reliable method for characterizing vesicles is vital for their use as model cell membranes in biophysics, synthetic biology, and origins of life studies. Instead of the traditionally used Rayleigh-Gans-Debye approximation, we use an exact extended Lorenz-Mie solution for how core-shell particles scatter light to model vesicle turbidity. This approach enables accurate interpretations of simple turbidimetric measurements and is able to accurately model highly scattering vesicles, such as larger vesicles, those with multiple layers, and those with encapsulated material. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.006DOI Listing
February 2019

Dynamic Exchange of Two Essential DNA Polymerases during Replication and after Fork Arrest.

Biophys J 2019 Feb 11;116(4):684-693. Epub 2019 Jan 11.

Department of Biophysics, University of Michigan, Ann Arbor, Michigan; Department of Chemistry, University of Michigan, Ann Arbor, Michigan. Electronic address:

The replisome is a multiprotein machine responsible for the faithful replication of chromosomal and plasmid DNA. Using single-molecule super-resolution imaging, we characterized the dynamics of three replisomal proteins in live Bacillus subtilis cells: the two replicative DNA polymerases, PolC and DnaE, and a processivity clamp loader subunit, DnaX. We quantified the protein mobility and dwell times during normal replication and following replication fork stress using damage-independent and damage-dependent conditions. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.008DOI Listing
February 2019

Size Matters: Ryanodine Receptor Cluster Size Heterogeneity Potentiates Calcium Waves.

Biophys J 2019 Feb 3;116(3):530-539. Epub 2019 Jan 3.

Department of Pharmacology, University of California Davis, Davis, California. Electronic address:

Ryanodine receptors (RyRs) mediate calcium (Ca)-induced Ca release and intracellular Ca homeostasis. In a cardiac myocyte, RyRs group into clusters of variable size from a few to several hundred RyRs, creating a spatially nonuniform intracellular distribution. It is unclear how heterogeneity of RyR cluster size alters spontaneous sarcoplasmic reticulum (SR) Ca releases (Ca sparks) and arrhythmogenic Ca waves. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369574PMC
February 2019

Probe Sensitivity to Cortical versus Intracellular Cytoskeletal Network Stiffness.

Biophys J 2019 Feb 7;116(3):518-529. Epub 2019 Jan 7.

Department of Biomedical Engineering, Northwestern University, Evanston, Illinois; Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Mechanical Engineering, Northwestern University, Evanston, Illinois. Electronic address:

In development, wound healing, and pathology, cell biomechanical properties are increasingly recognized as being of central importance. To measure these properties, experimental probes of various types have been developed, but how each probe reflects the properties of heterogeneous cell regions has remained obscure. To better understand differences attributable to the probe technology, as well as to define the relative sensitivity of each probe to different cellular structures, here we took a comprehensive approach. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369565PMC
February 2019
4 Reads

Pressure-Temperature Analysis of the Stability of the CTL9 Domain Reveals Hidden Intermediates.

Biophys J 2019 Feb 8;116(3):445-453. Epub 2019 Jan 8.

Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, New York. Electronic address:

The observation of two-state unfolding for many small single-domain proteins by denaturants has led to speculation that protein sequences may have evolved to limit the population of partially folded states that could be detrimental to fitness. How such strong cooperativity arises from a multitude of individual interactions is not well understood. Here, we investigate the stability and folding cooperativity of the C-terminal domain of the ribosomal protein L9 in the pressure-temperature plane using site-specific NMR. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369443PMC
February 2019
4 Reads
3.972 Impact Factor

Advances in Micropipette Aspiration: Applications in Cell Biomechanics, Models, and Extended Studies.

Biophys J 2019 Feb 7;116(4):587-594. Epub 2019 Jan 7.

Center for Biomedical Technology, Universidad Politécnica de Madrid, Pozuelo de Alarcón, Spain; Departamento de Ciencia de Materiales, ETSI de Caminos, Canales y Puertos, Universidad Politécnica de Madrid, Madrid, Spain. Electronic address:

With five decades of sustained application, micropipette aspiration has enabled a wide range of biomechanical studies in the field of cell mechanics. Here, we provide an update on the use of the technique, with a focus on recent developments in the analysis of the experiments, innovative microaspiration-based approaches, and applications in a broad variety of cell types. We first recapitulate experimental variations of the technique. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.004DOI Listing
February 2019
3.972 Impact Factor

Molecular Features of the Zn Binding Site in the Prion Protein Probed by Cd NMR.

Biophys J 2019 Feb 10;116(4):610-620. Epub 2019 Jan 10.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California. Electronic address:

The cellular prion protein (PrP) is a zinc-binding protein that contributes to the regulation of Zn and other divalent species of the central nervous system. Zn coordinates to the flexible, N-terminal repeat region of PrP and drives a tertiary contact between this repeat region and a well-defined cleft of the C-terminal domain. The tertiary structure promoted by Zn is thought to regulate inherent PrP toxicity. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.005DOI Listing
February 2019

Complex Phase Behavior of GUVs Containing Different Sphingomyelins.

Biophys J 2019 Feb 3;116(3):503-517. Epub 2019 Jan 3.

Istituto Nanoscienze CNR, S3, Modena, Italy; Dipartimento di Scienze Fisiche, Matematiche e Informatiche, Università di Modena e Reggio Emilia, Modena, Italy. Electronic address:

Understanding the lateral organization of biological membranes plays a key role on the road to fully appreciate the physiological functions of this fundamental barrier between the inside and outside regions of a cell. Ternary lipid bilayers composed of a high and a low melting temperature lipid and cholesterol represent a model system that mimics some of the important thermodynamical features of much more complex lipid mixtures such as those found in mammal membranes. The phase diagram of these ternary mixtures can be studied exploiting fluorescence microscopy in giant unilamellar vesicles, and it is typically expected to give rise, for specific combinations of composition and temperature, to regions of two-phase coexistence and a region with three-phase coexistence, namely, the liquid-ordered, liquid-disordered, and solid phases. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.018DOI Listing
February 2019
3.972 Impact Factor

Universal Kinetics of the Onset of Cell Spreading on Substrates of Different Stiffness.

Biophys J 2019 Feb 5;116(3):551-559. Epub 2019 Jan 5.

Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom. Electronic address:

When plated onto substrates, cell morphology and even stem-cell differentiation are influenced by the stiffness of their environment. Stiffer substrates give strongly spread (eventually polarized) cells with strong focal adhesions and stress fibers; very soft substrates give a less developed cytoskeleton and much lower cell spreading. The kinetics of this process of cell spreading is studied extensively, and important universal relationships are established on how the cell area grows with time. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369430PMC
February 2019

Magnetic Entropy as a Proposed Gating Mechanism for Magnetogenetic Ion Channels.

Biophys J 2019 Feb 8;116(3):454-468. Epub 2019 Jan 8.

Department of Electrical and Computer Engineering, Rice University, Houston, Texas; Department of Bioengineering, Rice University, Houston, Texas; Applied Physics Program, Rice University, Houston, Texas; Department of Neuroscience, Baylor College of Medicine, Houston, Texas. Electronic address:

Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of "magnetogenetic" ion channels based on biogenic ferritin nanoparticles have been questioned because known biophysical mechanisms cannot explain experimental observations. Here, we reproduce a weak magnetically mediated calcium response in HEK cells expressing a previously published TRPV4-ferritin fusion protein. We find that this magnetic sensitivity is attenuated when we reduce the temperature sensitivity of the channel but not when we reduce the mechanical sensitivity of the channel, suggesting that the magnetic sensitivity of this channel is thermally mediated. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369444PMC
February 2019
3.972 Impact Factor

Anisotropic Material Properties of Wild-Type and Tectb Tectorial Membranes.

Biophys J 2019 Feb 5;116(3):573-585. Epub 2019 Jan 5.

G.W.W. School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia. Electronic address:

The tectorial membrane (TM) is an extracellular matrix that is directly coupled with the mechanoelectrical receptors responsible for sensory transduction and amplification. As such, the TM is often hypothesized to play a key role in the remarkable sensory abilities of the mammalian cochlea. Genetic studies targeting TM proteins have shown that changes in TM structure dramatically affect cochlear function in mice. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369431PMC
February 2019
1 Read

A New Computational Method for Membrane Compressibility: Bilayer Mechanical Thickness Revisited.

Biophys J 2019 Feb 3;116(3):487-502. Epub 2019 Jan 3.

Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Greenberg Center, New York, New York.

Because lipid bilayers can bend and stretch in ways similar to thin elastic sheets, physical models of bilayer deformation have utilized mechanical constants such as the moduli for bending rigidity (κ) and area compressibility (K). However, the use of these models to quantify the energetics of membrane deformation associated with protein-membrane interactions, and the membrane response to stress is often hampered by the shortage of experimental data suitable for the estimation of the mechanical constants of various lipid mixtures. Although computational tools such as molecular dynamics simulations can provide alternative means to estimate K values, current approaches suffer significant technical limitations. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369663PMC
February 2019

β-Branched Amino Acids Stabilize Specific Conformations of Cyclic Hexapeptides.

Biophys J 2019 Feb 3;116(3):433-444. Epub 2019 Jan 3.

Department of Chemistry, Tufts University, Medford, Massachusetts. Electronic address:

Cyclic peptides (CPs) are a promising class of molecules for drug development, particularly as inhibitors of protein-protein interactions. Predicting low-energy structures and global structural ensembles of individual CPs is critical for the design of bioactive molecules, but these are challenging to predict and difficult to verify experimentally. In our previous work, we used explicit-solvent molecular dynamics simulations with enhanced sampling methods to predict the global structural ensembles of cyclic hexapeptides containing different permutations of glycine, alanine, and valine. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00063495183452
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http://dx.doi.org/10.1016/j.bpj.2018.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369414PMC
February 2019
5 Reads

The Interplay of Structural and Cellular Biophysics Controls Clustering of Multivalent Molecules.

Biophys J 2019 Feb 7;116(3):560-572. Epub 2019 Jan 7.

Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, Connecticut. Electronic address:

Dynamic molecular clusters are assembled through weak multivalent interactions and are platforms for cellular functions, especially receptor-mediated signaling. Clustering is also a prerequisite for liquid-liquid phase separation. It is not well understood, however, how molecular structure and cellular organization control clustering. Read More

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http://dx.doi.org/10.1016/j.bpj.2019.01.001DOI Listing
February 2019
1 Read

Influence of Transmembrane Helix Mutations on Cytochrome P450-Membrane Interactions and Function.

Biophys J 2019 Feb 3;116(3):419-432. Epub 2019 Jan 3.

Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany; Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany; Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany. Electronic address:

Human cytochrome P450 (CYP) enzymes play an important role in the metabolism of drugs, steroids, fatty acids, and xenobiotics. Microsomal CYPs are anchored in the endoplasmic reticulum membrane by an N-terminal transmembrane (TM) helix that is connected to the globular catalytic domain by a flexible linker sequence. However, the structural and functional importance of the TM-helix is unclear because it has been shown that CYPs can still associate with the membrane and have enzymatic activity in reconstituted systems after truncation or modification of the N-terminal sequence. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00063495183452
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http://dx.doi.org/10.1016/j.bpj.2018.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369400PMC
February 2019
5 Reads
3.972 Impact Factor

Cryo-Cooling Effect on DHFR Crystal Studied by Replica-Exchange Molecular Dynamics Simulations.

Biophys J 2019 Feb 13;116(3):395-405. Epub 2018 Dec 13.

RIKEN Center for Computational Science, Kobe, Hyogo, Japan. Electronic address:

Cryo-cooling is routinely performed before x-ray diffraction image collection to reduce the damage to crystals due to ionizing radiation. It has been suggested that although backbone structures are usually very similar between room temperature and cryo-temperature, cryo-cooling may hamper biologically relevant dynamics. In this study, the crystal of Escherichia coli dihydrofolate reductase is studied with replica-exchange molecular dynamics simulation, and the results are compared with the crystal structure determined at cryo-temperature and room temperature with the time-averaged ensemble method. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.11.3139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369401PMC
February 2019
2 Reads

Rickettsia Sca2 Recruits Two Actin Subunits for Nucleation but Lacks WH2 Domains.

Biophys J 2019 Feb 18;116(3):540-550. Epub 2018 Dec 18.

Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

The Rickettsia ∼1800-amino-acid autotransporter protein surface cell antigen 2 (Sca2) promotes actin polymerization on the surface of the bacterium to drive its movement using an actin comet-tail mechanism. Sca2 mimics eukaryotic formins in that it promotes both actin filament nucleation and elongation and competes with capping protein to generate filaments that are long and unbranched. However, despite these functional similarities, Sca2 is structurally unrelated to eukaryotic formins and achieves these functions through an entirely different mechanism. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369429PMC
February 2019
2 Reads

Automatic Detection and Classification of Ca Release Events in Line- and Frame-Scan Images.

Biophys J 2019 Feb 25;116(3):383-394. Epub 2018 Dec 25.

Department of Physiology, University of Bern, Bern, Switzerland. Electronic address:

Analysis of Ca signals obtained in various cell types (i.e., cardiomyocytes) is always a tradeoff between acquisition speed and signal/noise ratio of the fluorescence signal. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369403PMC
February 2019
1 Read

How Fluorescent Tags Modify Oligomer Size Distributions of the Alzheimer Peptide.

Biophys J 2019 Jan 19;116(2):227-238. Epub 2018 Dec 19.

Department of Biotechnology and Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany. Electronic address:

Within the complex aggregation process of amyloidogenic peptides into fibrils, early stages of aggregation play a central role and reveal fundamental properties of the underlying mechanism of aggregation. In particular, low-molecular-weight aggregates of the Alzheimer amyloid-β peptide (Aβ) have attracted increasing interest because of their role in cytotoxicity and neuronal apoptosis, typical of aggregation-related diseases. One of the main techniques used to characterize oligomeric stages is fluorescence spectroscopy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00063495183450
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http://dx.doi.org/10.1016/j.bpj.2018.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350010PMC
January 2019
2 Reads

The Mechanical Properties of RNA-DNA Hybrid Duplex Stretched by Magnetic Tweezers.

Biophys J 2019 Jan 13;116(2):196-204. Epub 2018 Dec 13.

College of Life Sciences, the Institute for Advanced Studies, State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, China. Electronic address:

RNA can anneal to its DNA template to generate an RNA-DNA hybrid (RDH) duplex and a displaced DNA strand, termed R-loop. RDH duplex occupies up to 5% of the mammalian genome and plays important roles in many biological processes. The functions of RDH duplex are affected by its mechanical properties, including the elasticity and the conformation transitions. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350079PMC
January 2019
1 Read
3.972 Impact Factor

Three-Dimensional Cell Geometry Controls Excitable Membrane Signaling in Dictyostelium Cells.

Biophys J 2019 Jan 20;116(2):372-382. Epub 2018 Dec 20.

Laboratory for Physical Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan. Electronic address:

Phosphatidylinositol (3-5)-trisphosphate (PtdInsP3) is known to propagate as waves on the plasma membrane and is related to the membrane-protrusive activities in Dictyostelium and mammalian cells. Although there have been a few attempts to study the three-dimensional (3D) dynamics of these processes, most studies have focused on the dynamics extracted from single focal planes. However, the relation between the dynamics and 3D cell shape remains elusive because of the lack of signaling information about the unobserved part of the membrane. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350023PMC
January 2019
1 Read

Fosfomycin Permeation through the Outer Membrane Porin OmpF.

Biophys J 2019 Jan 8;116(2):258-269. Epub 2018 Dec 8.

Department of Physics and Earth Sciences, Jacobs University Bremen, Bremen, Germany. Electronic address:

Fosfomycin is a frequently prescribed drug in the treatment of acute urinary tract infections. It enters the bacterial cytoplasm and inhibits the biosynthesis of peptidoglycans by targeting the MurA enzyme. Despite extensive pharmacological studies and clinical use, the permeability of fosfomycin across the bacterial outer membrane is largely unexplored. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350074PMC
January 2019
1 Read

Molecular Mechanisms of Macular Degeneration Associated with the Complement Factor H Y402H Mutation.

Biophys J 2019 Jan 14;116(2):215-226. Epub 2018 Dec 14.

Department of Bioengineering, University of California, Riverside, Riverside, California. Electronic address:

A single nucleotide polymorphism, tyrosine at position 402 to histidine (Y402H), within the gene encoding complement factor H (FH) predisposes individuals to acquiring age-related macular degeneration (AMD) after aging. This polymorphism occurs in short consensus repeat (SCR) 7 of FH and results in decreased binding affinity of SCR6-8 for heparin. As FH is responsible for regulating the complement system, decreased affinity for heparin results in decreased regulation on surfaces of self. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350009PMC
January 2019
1 Read

Dynamics of Membrane-Bound G12V-KRAS from Simulations and Single-Molecule FRET in Native Nanodiscs.

Biophys J 2019 Jan 20;116(2):179-183. Epub 2018 Dec 20.

Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; Biochemistry and Cell Biology Program, MD Anderson University of Texas Health Science Center at Houston, Graduate School of Biochemical Sciences, Houston, Texas. Electronic address:

Recent studies have shown that the small GTPase KRAS adopts multiple orientations with respect to the plane of anionic model membranes, whereby either the three C-terminal helices or the three N-terminal β-strands of the catalytic domain face the membrane. This has functional implications because, in the latter, the membrane occludes the effector-interacting surface. However, it remained unclear how membrane reorientation occurs and, critically, whether it occurs in the cell in which KRAS operates as a molecular switch in signaling pathways. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350008PMC
January 2019
1 Read
3.972 Impact Factor