Potential Hydrodynamic Cytoplasmic Transfer between Mammalian Cells: Cell-Projection Pumping.
PMID: 32234501 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - March 31, 2020 Category: Physics Authors: Zoellner H, Paknejad N, Cornwell J, Chami B, Romin Y, Boyko V, Fujisawa S, Kelly E, Lynch GW, Rogers G, Manova K, Moore MAS Tags: Biophys J Source Type: research

Protein Structure Prediction and Design in a Biologically Realistic Implicit Membrane.
Abstract Protein design is a powerful tool for elucidating mechanisms of function and engineering new therapeutics and nanotechnologies. Although soluble protein design has advanced, membrane protein design remains challenging because of difficulties in modeling the lipid bilayer. In this work, we developed an implicit approach that captures the anisotropic structure, shape of water-filled pores, and nanoscale dimensions of membranes with different lipid compositions. The model improves performance in computational benchmarks against experimental targets, including prediction of protein orientations in the bilayer...
Source: Biophysical Journal - March 14, 2020 Category: Physics Authors: Alford RF, Fleming PJ, Fleming KG, Gray JJ Tags: Biophys J Source Type: research

Mechanical Regulation of Neurite Polarization and  Growth: A Computational Study.
Mechanical Regulation of Neurite Polarization and Growth: A Computational Study. Biophys J. 2020 Mar 14;: Authors: Jakobs MAH, Franze K, Zemel A Abstract The densely packed microtubule (MT) array found in neuronal cell projections (neurites) serves two fundamental functions simultaneously: it provides a mechanically stable track for molecular motor-based transport and produces forces that drive neurite growth. The local pattern of MT polarity along the neurite shaft has been found to differ between axons and dendrites. In axons, the neurons' dominating long projections, roughly 90% of the MTs ori...
Source: Biophysical Journal - March 14, 2020 Category: Physics Authors: Jakobs MAH, Franze K, Zemel A Tags: Biophys J Source Type: research

Measuring Stepwise Binding of Thermally Fluctuating Particles to Cell Membranes without Fluorescence.
Abstract Thermal motions enable a particle to probe the optimal interaction state when binding to a cell membrane. However, especially on the scale of microseconds and nanometers, position and orientation fluctuations are difficult to observe with common measurement technologies. Here, we show that it is possible to detect single binding events of immunoglobulin-G-coated polystyrene beads, which are held in an optical trap near the cell membrane of a macrophage. Changes in the spatial and temporal thermal fluctuations of the particle were measured interferometrically, and no fluorophore labeling was required. We d...
Source: Biophysical Journal - March 14, 2020 Category: Physics Authors: Rohrbach A, Meyer T, Stelzer EHK, Kress H Tags: Biophys J Source Type: research

The Kinesin-8 Kip3 Depolymerizes Microtubules with a Collective Force-Dependent Mechanism.
h A Abstract Microtubules are highly dynamic filaments with dramatic structural rearrangements and length changes during the cell cycle. An accurate control of the microtubule length is essential for many cellular processes, in particular during cell division. Motor proteins from the kinesin-8 family depolymerize microtubules by interacting with their ends in a collective and length-dependent manner. However, it is still unclear how kinesin-8 depolymerizes microtubules. Here, we tracked the microtubule end-binding activity of yeast kinesin-8, Kip3, under varying loads and nucleotide conditions using high-precision...
Source: Biophysical Journal - March 14, 2020 Category: Physics Authors: Bugiel M, Chugh M, Jachowski TJ, Schäffer E, Jannasch A Tags: Biophys J Source Type: research

Presence or Absence of Ras Dimerization Shows Distinct Kinetic Signature in Ras-Raf Interaction.
;a AE Abstract Initiations of cell signaling pathways often occur through the formation of multiprotein complexes that form through protein-protein interactions. Therefore, detecting their presence is central to understanding the function of a cell signaling pathway, aberration of which often leads to fatal diseases, including cancers. However, the multiprotein complexes are often difficult to detect using microscopes due to their small sizes. Therefore, currently, their presence can be only detected through indirect means. In this article, we propose to investigate the presence or absence of protein complexes thr...
Source: Biophysical Journal - March 14, 2020 Category: Physics Authors: Sarkar S, García AE Tags: Biophys J Source Type: research

Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1.
Abstract The folding reaction of a stable monomeric variant of Cu/Zn superoxide dismutase (mSOD1), an enzyme responsible for the conversion of superoxide free radicals into hydrogen peroxide and oxygen, is known to be among the slowest folding processes that adhere to two-state behavior. The long lifetime, ∼10 s, of the unfolded state presents ample opportunities for the polypeptide chain to transiently sample nonnative structures before the formation of the productive folding transition state. We recently observed the formation of a nonnative structure in a peptide model of the C-terminus of SOD1, a sequence ...
Source: Biophysical Journal - March 12, 2020 Category: Physics Authors: Cohen NR, Kayatekin C, Zitzewitz JA, Bilsel O, Matthews CR Tags: Biophys J Source Type: research

PIE-FLIM Measurements of Two Different FRET-Based Biosensor Activities in the Same Living Cells.
We report the use of pulsed interleaved excitation (PIE)-fluorescence lifetime imaging microscopy (FLIM) to measure the activities of two different biosensor probes simultaneously in single living cells. Many genetically encoded biosensors rely on the measurement of Förster resonance energy transfer (FRET) to detect changes in biosensor conformation that accompany the targeted cell signaling event. One of the most robust ways of quantifying FRET is to measure changes in the fluorescence lifetime of the donor fluorophore using FLIM. The study of complex signaling networks in living cells demands the ability to track mo...
Source: Biophysical Journal - March 10, 2020 Category: Physics Authors: Reissaus CA, Day KH, Mirmira RG, Dunn KW, Pavalko FM, Day RN Tags: Biophys J Source Type: research

Soft Power of Nonconsensus Protein-DNA Binding.
PMID: 32187530 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - March 4, 2020 Category: Physics Authors: Teif VB Tags: Biophys J Source Type: research

Myosin II Filament Dynamics in Actin Networks Revealed with Interferometric Scattering Microscopy.
DV Abstract The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood because of difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and ...
Source: Biophysical Journal - March 4, 2020 Category: Physics Authors: Mosby LS, Hundt N, Young G, Fineberg A, Polin M, Mayor S, Kukura P, Köster DV Tags: Biophys J Source Type: research

What Makes a Good Pore Former: A Study of Synthetic Melittin Derivatives.
Abstract Pore formation by membrane-active peptides, naturally encountered in innate immunity and infection, could have important medical and technological applications. Recently, the well-studied lytic peptide melittin has formed the basis for the development of combinatorial libraries from which potent pore-forming peptides have been derived, optimized to work under different conditions. We investigate three such peptides, macrolittin70, which is most active at neutral pH; pHD15, which is active only at low pH; and MelP5_Δ6, which was rationally designed to be active at low pH but formed only small pores. ...
Source: Biophysical Journal - March 3, 2020 Category: Physics Authors: Sepehri A, PeBenito L, Pino-Angeles A, Lazaridis T Tags: Biophys J Source Type: research

Microrheology for Hi-C Data Reveals the Spectrum of the Dynamic 3D Genome Organization.
Abstract The one-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in a three-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multiscale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments have revealed the dynamic organization of chromatin domains caused by stochastic thermal fluctuations. However, the mechanism underlying the dynamic regulation of such hierarchical and structur...
Source: Biophysical Journal - March 3, 2020 Category: Physics Authors: Shinkai S, Sugawara T, Miura H, Hiratani I, Onami S Tags: Biophys J Source Type: research

Kindlin Assists Talin to Promote Integrin Activation.
Abstract Integrin αIIbβ3 is a predominant type of integrin abundantly expressed on the surface of platelets and its activation regulates the process of thrombosis. Talin and kindlin are cytoplasmic proteins that bind to integrin and modulate its affinity for extracellular ligands. Although the molecular details of talin-mediated integrin activation are known, the mechanism of kindlin involvement in this process remains elusive. Here, we demonstrate that the interplay between talin and kindlin promotes integrin activation. Our all-atomic molecular dynamics simulations on complete transmembrane and cytopl...
Source: Biophysical Journal - March 3, 2020 Category: Physics Authors: Haydari Z, Shams H, Jahed Z, Mofrad MRK Tags: Biophys J Source Type: research

Simple, but Not Too Simple: Modeling the Dynamics of DNA and RNA Buckling.
on; F PMID: 32171419 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - March 3, 2020 Category: Physics Authors: Lankaš F Tags: Biophys J Source Type: research

Genome Dashboards: Framework and Examples.
Abstract Genomics is a sequence-based informatics science and a three-dimensional-structure-based material science. However, in practice, most genomics researchers utilize sequence-based informatics approaches or three-dimensional-structure-based material science techniques, not both. This division is, at least in part, the result of historical developments rather than a fundamental necessity. The underlying computational tools, experimental techniques, and theoretical models were developed independently. The primary result presented here is a framework for the unification of informatics- and physics-based data as...
Source: Biophysical Journal - February 29, 2020 Category: Physics Authors: Li Z, Sun R, Bishop TC Tags: Biophys J Source Type: research

Spiral Wave Propagation in Communities with Spatially Correlated Heterogeneity.
r A Abstract Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable wave propagation in a two-dimensional heterogeneous community. The model shows three dynamic regimes in which waves either propagate directionally, die out, or spiral indefinitely, and we characterize how these regimes depend on the heterogeneity parameters. We find that in some parameter...
Source: Biophysical Journal - February 26, 2020 Category: Physics Authors: Zhai X, Larkin JW, Süel GM, Mugler A Tags: Biophys J Source Type: research

Shining Light on the Mode and Mechanism of Vesicular Release at Rod Photoreceptor Synapse.
PMID: 32101707 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - February 25, 2020 Category: Physics Authors: Sinha R Tags: Biophys J Source Type: research

Transcription Factor Binding in Embryonic Stem Cells Is Constrained by DNA Sequence Repeat Symmetry.
Abstract Transcription factor (TF) recognition is dictated by the underlying DNA motif sequence specific for each TF. Here, we reveal that DNA sequence repeat symmetry plays a central role in defining TF-DNA-binding preferences. In particular, we find that different TFs bind similar symmetry patterns in the context of different developmental layers. Most TFs possess dominant preferences for similar DNA repeat symmetry types. However, in some cases, preferences of specific TFs are changed during differentiation, suggesting the importance of information encoded outside of known motif regions. Histone modifications a...
Source: Biophysical Journal - February 15, 2020 Category: Physics Authors: Goldshtein M, Mellul M, Deutch G, Imashimizu M, Takeuchi K, Meshorer E, Ram O, Lukatsky DB Tags: Biophys J Source Type: research

Recruitment of Ubiquitin within an E2 Chain Elongation Complex.
Abstract The ubiquitin (Ub) proteolysis pathway uses an E1, E2, and E3 enzyme cascade to label substrate proteins with ubiquitin and target them for degradation. The mechanisms of ubiquitin chain formation remain unclear and include a sequential addition model, in which polyubiquitin chains are built unit by unit on the substrate, or a preassembly model, in which polyubiquitin chains are preformed on the E2 or E3 enzyme and then transferred in one step to the substrate. The E2 conjugating enzyme UBE2K has a 150-residue catalytic core domain and a C-terminal ubiquitin-associated (UBA) domain. Polyubiquitin chains a...
Source: Biophysical Journal - February 15, 2020 Category: Physics Authors: Cook BW, Lacoursiere RE, Shaw GS Tags: Biophys J Source Type: research

Cell Fate Forecasting: A Data-Assimilation Approach to Predict Epithelial-Mesenchymal Transition.
In this study, we demonstrate that a data-assimilation approach using an ensemble Kalman filter, which combines limited noisy observations with predictions from a computational model of TGFβ-induced EMT, can reconstruct the cell state and predict the timing of state transitions. We used our approach in proof-of-concept "synthetic" in silico experiments, in which experimental observations were produced from a known computational model with the addition of noise. We mimic parameter uncertainty in in vitro experiments by incorporating model error that shifts the TGFβ doses associated with the sta...
Source: Biophysical Journal - February 15, 2020 Category: Physics Authors: Mendez MJ, Hoffman MJ, Cherry EM, Lemmon CA, Weinberg SH Tags: Biophys J Source Type: research

Facile Characterization of Topology of DNA Catenanes.
Abstract During the preparation of single-stranded DNA catenanes, topological isomers of different linking numbers (Lk) are intrinsically produced, and they must be separated from each other to construct sophisticated nanostructures accurately. In many previous studies, however, mixtures of these isomers were directly employed to construct nanostructures without sufficient characterization. Here, we present a method that easily and clearly characterizes the isomers by polyacrylamide gel electrophoresis. To the mixtures of topological isomers of [2]catenanes, two-strut oligonucleotides, which are complementary with...
Source: Biophysical Journal - February 15, 2020 Category: Physics Authors: Li L, An R, Tang J, Sui Z, Wang G, Komiyama M, Liang X Tags: Biophys J Source Type: research

Spatially Discordant Repolarization Alternans in the Absence of Conduction Velocity Restitution.
In this study, we carried out computer simulations using mathematical models of action potentials to investigate the mechanisms of SDA in cardiac tissue. We show that when CVR is present and engaged, such as fast pacing from one side of the tissue, the spatial pattern of APD in the tissue undergoes either spatially concordant alternans or SDA, independent of initial conditions or tissue heterogeneities. When CVR is not engaged, such as simultaneous pacing of the whole tissue or under normal/slow heart rates, the spatial pattern of APD in the tissue can have multiple solutions, including spatially concordant alternans and d...
Source: Biophysical Journal - February 15, 2020 Category: Physics Authors: Huang C, Song Z, Landaw J, Qu Z Tags: Biophys J Source Type: research

Biophysics of Membrane Protein Signaling.
PMID: 32061271 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - February 14, 2020 Category: Physics Authors: Plested A, Jayaraman V Tags: Biophys J Source Type: research

"Stochastic Resonance" for Individual Cells.
"Stochastic Resonance" for Individual Cells. Biophys J. 2020 Feb 04;118(3):533-534 Authors: Riveline D, Lo Vecchio S PMID: 32023439 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - February 4, 2020 Category: Physics Authors: Riveline D, Lo Vecchio S Tags: Biophys J Source Type: research

Differential or Curvature Stress? Modus Vivendi.
PMID: 32023440 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - February 4, 2020 Category: Physics Authors: Lyman E, Sodt AJ Tags: Biophys J Source Type: research

Zig Zag AFM Protocol Reveals New Intermediate Folding States of Bacteriorhodopsin.
PMID: 32023441 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - February 4, 2020 Category: Physics Authors: Nash MA Tags: Biophys J Source Type: research

Electrostatics of Prokaryotic Ribosome and Its Biological Implication.
Abstract Ribosomes are essential machines for protein synthesis in cells. Their structures are very complex but conserved in different species. Because most parts of a ribosome are composed of negatively charged RNAs, its electrostatics should play a fundamental role in the realization of its functions. However, a complete picture of the electrostatics of ribosomes is still absent at present. Here, assisted by the latest version of DelPhi (version 8.4), we illustrate a picture of the electrostatics of a prokaryotic ribosome as well as its molecular chaperones. The revealed electrostatics features are consistent wi...
Source: Biophysical Journal - January 23, 2020 Category: Physics Authors: Wang J, Karki C, Xiao Y, Li L Tags: Biophys J Source Type: research

Classifying Drugs by their Arrhythmogenic Risk Using Machine Learning.
Abstract All medications have adverse effects. Among the most serious of these are cardiac arrhythmias. Current paradigms for drug safety evaluation are costly, lengthy, conservative, and impede efficient drug development. Here, we combine multiscale experiment and simulation, high-performance computing, and machine learning to create a risk estimator to stratify new and existing drugs according to their proarrhythmic potential. We capitalize on recent developments in machine learning and integrate information across 10 orders of magnitude in space and time to provide a holistic picture of the effects of drugs, ei...
Source: Biophysical Journal - January 22, 2020 Category: Physics Authors: Sahli-Costabal F, Seo K, Ashley E, Kuhl E Tags: Biophys J Source Type: research

Membrane-Bound Ras as a Conformational Clock.
PMID: 32023437 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - January 22, 2020 Category: Physics Authors: Gorfe AA, Sligar SG Tags: Biophys J Source Type: research

On the Long and Winding Road to a Perfect Membrane Model.
PMID: 31968235 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - January 21, 2020 Category: Physics Authors: Doktorova M Tags: Biophys J Source Type: research

Nervous Tissue Stiffens Postinjury.
PMID: 31968236 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - January 21, 2020 Category: Physics Authors: Kuhl E Tags: Biophys J Source Type: research

Tasting the Terroir with Tsr.
PMID: 31968237 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - January 21, 2020 Category: Physics Authors: Podgorny AR, Ray JCJ Tags: Biophys J Source Type: research

Straightening Out the Elasticity of Myosin Cross-Bridges.
Abstract In a contracting muscle, myosin cross-bridges extending from thick filaments pull the interdigitating thin (actin-containing) filaments during cyclical ATP-driven interactions toward the center of the sarcomere, the structural unit of striated muscle. Cross-bridge attachments in the sarcomere have been reported to exhibit a similar stiffness under both positive and negative forces. However, in vitro measurements on filaments with a sparse complement of heads detected a decrease of the cross-bridge stiffness at negative forces attributed to the buckling of the subfragment 2 tail portion. Here, we revi...
Source: Biophysical Journal - January 13, 2020 Category: Physics Authors: Linari M, Piazzesi G, Pertici I, Dantzig JA, Goldman YE, Lombardi V Tags: Biophys J Source Type: research

Three Beads Are Better Than One.
PMID: 31951531 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - January 7, 2020 Category: Physics Authors: Howard J, Hancock WO Tags: Biophys J Source Type: research

Dynamics of Membrane-Bound G12V-KRAS from Simulations and Single-Molecule FRET in Native Nanodiscs.
PMID: 31924346 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - January 7, 2020 Category: Physics Authors: Prakash P, Litwin D, Liang H, Sarkar-Banerjee S, Dolino D, Zhou Y, Hancock JF, Jayaraman V, Gorfe AA Tags: Biophys J Source Type: research

Mapping Multiple Distances in a Multidomain Protein for the Identification of Folding Intermediates.
r J Abstract The investigation and understanding of the folding mechanism of multidomain proteins is still a challenge in structural biology. The use of single-molecule Förster resonance energy transfer offers a unique tool to map conformational changes within the protein structure. Here, we present a study following denaturant-induced unfolding transitions of yeast phosphoglycerate kinase by mapping several inter- and intradomain distances of this two-domain protein, exhibiting a quite heterogeneous behavior. On the one hand, the development of the interdomain distance during the unfolding transition suggest...
Source: Biophysical Journal - December 18, 2019 Category: Physics Authors: Cerminara M, Schöne A, Ritter I, Gabba M, Fitter J Tags: Biophys J Source Type: research

Rapid Simulation of Unprocessed DEER Decay Data for Protein Fold Prediction.
Abstract Despite advances in sampling and scoring strategies, Monte Carlo modeling methods still struggle to accurately predict de novo the structures of large proteins, membrane proteins, or proteins of complex topologies. Previous approaches have addressed these shortcomings by leveraging sparse distance data gathered using site-directed spin labeling and electron paramagnetic resonance spectroscopy to improve protein structure prediction and refinement outcomes. However, existing computational implementations entail compromises between coarse-grained models of the spin label that lower the resolution and explic...
Source: Biophysical Journal - December 18, 2019 Category: Physics Authors: Del Alamo D, Tessmer MH, Stein RA, Feix JB, Mchaourab HS, Meiler J Tags: Biophys J Source Type: research

Remodeling Promotes Proarrhythmic Disruption of Calcium Homeostasis in Failing Atrial Myocytes.
In this study, we apply a multiscale computational framework to establish a mechanistic link between atrial myocyte structural remodeling in HF and AF. Using a spatially distributed model of calcium (Ca) signaling, we show that disruption of the spatial relationship between L-type Ca channels (LCCs) and ryanodine receptors results in markedly increased Ca content of the sarcoplasmic reticulum (SR). This increase in SR load is due to changes in the balance between Ca entry via LCCs and Ca extrusion due to the sodium-calcium exchanger after an altered spatial relationship between these signaling proteins. Next, we show that ...
Source: Biophysical Journal - December 18, 2019 Category: Physics Authors: Shiferaw Y, Aistrup GL, Louch WE, Wasserstrom JA Tags: Biophys J Source Type: research

Cardiomyopathy Mutation Alters End-to-End Junction of Tropomyosin and Reduces Calcium Sensitivity.
Abstract Muscle contraction is governed by tropomyosin (Tpm) shifting azimuthally between three states on F-actin (B-, C-, and M-states) in response to calcium binding to troponin and actomyosin cross-bridge formation. The Tpm coiled coil polymerizes head to tail along the long-pitch helix of F-actin to form continuous superhelical cables that wrap around the actin filaments. The end-to-end bonds formed between the N- and C-terminus of adjacent Tpm molecules define Tpm continuity and play a critical role in the ability of Tpm to cooperatively bind to actin, thus facilitating Tpm conformational switching to co...
Source: Biophysical Journal - December 14, 2019 Category: Physics Authors: Sundar S, Rynkiewicz MJ, Ghosh A, Lehman W, Moore JR Tags: Biophys J Source Type: research

Ligand Entry into Fatty Acid Binding Protein via Local Unfolding Instead of Gap Widening.
Abstract Fatty acid binding proteins play an important role in the transportation of fatty acids. Despite intensive studies, how fatty acids enter the protein cavity for binding is still controversial. Here, a gap-closed variant of human intestinal fatty acid binding protein was generated by mutagenesis, in which the gap is locked by a disulfide bridge. According to its structure determined here by NMR, this variant has no obvious openings as the ligand entrance and the gap cannot be widened by internal dynamics. Nevertheless, it still takes up fatty acids and other ligands. NMR relaxation dispersion, chemical exc...
Source: Biophysical Journal - December 14, 2019 Category: Physics Authors: Xiao T, Lu Y, Fan JS, Yang D Tags: Biophys J Source Type: research

Sensitive Detection of Protein Binding to the Plasma Membrane with Dual-Color Z-Scan Fluorescence.
Abstract Delicate and transitory protein engagement at the plasma membrane (PM) is crucial to a broad range of cellular functions, including cell motility, signal transduction, and virus replication. Here, we describe a dual-color (DC) extension of the fluorescence z-scan technique, which has proven successful for quantification of peripheral membrane protein binding to the PM in living cells. We demonstrate that the coexpression of a second, distinctly colored fluorescent protein provides a soluble reference species that delineates the extent of the cell cytoplasm and lowers the detection threshold of z-scan PM-b...
Source: Biophysical Journal - December 12, 2019 Category: Physics Authors: Angert I, Karuka SR, Hennen J, Chen Y, Albanesi JP, Mansky LM, Mueller JD Tags: Biophys J Source Type: research

Zebrafish Spinal Cord Repair Is Accompanied by Transient Tissue Stiffening.
k J Abstract Severe injury to the mammalian spinal cord results in permanent loss of function due to the formation of a glial-fibrotic scar. Both the chemical composition and the mechanical properties of the scar tissue have been implicated to inhibit neuronal regrowth and functional recovery. By contrast, adult zebrafish are able to repair spinal cord tissue and restore motor function after complete spinal cord transection owing to a complex cellular response that includes axon regrowth and is accompanied by neurogenesis. The mechanical mechanisms contributing to successful spinal cord repair in adult zebrafish a...
Source: Biophysical Journal - December 7, 2019 Category: Physics Authors: Möllmert S, Kharlamova MA, Hoche T, Taubenberger AV, Abuhattum S, Kuscha V, Kurth T, Brand M, Guck J Tags: Biophys J Source Type: research

The Reactions of O2 and NO with Mixed-Valence ba3 Cytochrome c Oxidase from Thermus thermophilus.
ir Ó Abstract Earlier CO flow-flash experiments on the fully reduced Thermus thermophilus ba3 (Tt ba3) cytochrome oxidase revealed that O2 binding was slowed down by a factor of 10 in the presence of CO (Szundi et al., 2010, PNAS 107, 21010-21015). The goal of the current study is to explore whether the long apparent lifetime (∼50 ms) of the CuB+-CO complex generated upon photolysis of the CO-bound mixed-valence Tt ba3 (Koutsoupakis et al., 2019, Acc. Chem. Res. 52, 1380-1390) affects O2 and NO binding and the ability of CuB to act as an electron donor during O-O bond splitting. The CO re...
Source: Biophysical Journal - December 6, 2019 Category: Physics Authors: Szundi I, Funatogawa C, Soulimane T, Einarsdóttir Ó Tags: Biophys J Source Type: research

Docking Troponin T onto the Tropomyosin Overlapping Domain of Thin Filaments.
Abstract Complete description of thin filament conformational transitions accompanying muscle regulation requires ready access to atomic structures of actin-bound tropomyosin-troponin. To date, several molecular-docking protocols have been employed to identify troponin interactions on actin-tropomyosin because high-resolution experimentally determined structures of filament-associated troponin are not available. However, previously published all-atom models of the thin filament show chain separation and corruption of components during our molecular dynamics simulations of the models, implying artifactual subunit o...
Source: Biophysical Journal - December 6, 2019 Category: Physics Authors: Pavadai E, Rynkiewicz MJ, Ghosh A, Lehman W Tags: Biophys J Source Type: research

Structure of an Unfolding Intermediate of an RRM Domain of ETR-3 Reveals Its Native-like Fold.
Abstract Prevalence of one or more partially folded intermediates during protein unfolding with different secondary and ternary conformations has been identified as an integral character of protein unfolding. These transition-state species need to be characterized structurally for elucidation of their folding pathways. We have determined the three-dimensional structure of an intermediate state with increased conformational space sampling under urea-denaturing condition. The protein unfolds completely at 10 M urea but retains residual secondary structural propensities with restricted motion. Here, we describe ...
Source: Biophysical Journal - December 6, 2019 Category: Physics Authors: Bhatt H, Ganguly AK, Sharma S, Kushwaha GS, Firoz Khan M, Sen S, Bhavesh NS Tags: Biophys J Source Type: research

Area and Geometry Dependence of Cell Migration in Asymmetric Two-State Micropatterns.
uml;dler JO Abstract Microstructured surfaces provide a unique framework to probe cell migration and cytoskeletal dynamics in a standardized manner. Here, we report on the steady-state occupancy probability of cells in asymmetric two-state microstructures that consist of two fibronectin-coated adhesion sites connected by a thin guidance cue. In these dumbbell-like structures, cells transition between the two sites in a repeated and stochastic manner, and average dwell times in the respective microenvironments are determined from the cell trajectories. We study the dynamics of human breast carcinoma cells (MDA-MB-2...
Source: Biophysical Journal - November 29, 2019 Category: Physics Authors: Fink A, Brückner DB, Schreiber C, Röttgermann PJF, Broedersz CP, Rädler JO Tags: Biophys J Source Type: research

Structural Basis of Enhanced Facilitated Diffusion of DNA-Binding Protein in Crowded Cellular Milieu.
Abstract Although the fast association between DNA-binding proteins (DBPs) and DNA is explained by a facilitated diffusion mechanism, in which DBPs adopt a weighted combination of three-dimensional diffusion and one-dimensional (1D) sliding and hopping modes of transportation, the role of cellular environment that contains many nonspecifically interacting proteins and other biomolecules is mostly overlooked. By performing large-scale computational simulations with an appropriately tuned model of protein and DNA in the presence of nonspecifically interacting bulk and DNA-bound crowders (genomic crowders), we demons...
Source: Biophysical Journal - November 29, 2019 Category: Physics Authors: Dey P, Bhattacherjee A Tags: Biophys J Source Type: research

The Heart by Numbers.
PMID: 31791548 [PubMed - as supplied by publisher] (Source: Biophysical Journal)
Source: Biophysical Journal - November 29, 2019 Category: Physics Authors: Campbell KS, Beard DA, Qu Z Tags: Biophys J Source Type: research

The Bilayer Collective Properties Govern the Interaction of an HIV-1 Antibody with the Viral Membrane.
jo-Isidro J Abstract Efficient engagement with the envelope glycoprotein membrane-proximal external region (MPER) results in robust blocking of viral infection by a class of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV). Developing an accommodation surface that engages with the viral lipid envelope appears to correlate with the neutralizing potency displayed by these bnAbs. The nature of the interactions established between the antibody and the lipid is nonetheless a matter of debate, with some authors arguing that anti-MPER specificity arises only under pathological conditions...
Source: Biophysical Journal - November 14, 2019 Category: Physics Authors: Carravilla P, Darré L, Oar-Arteta IR, Vesga AG, Rujas E, de Las Heras-Martínez G, Domene C, Nieva JL, Requejo-Isidro J Tags: Biophys J Source Type: research

Kinetic Mechanisms of Fast Glutamate Sensing by Fluorescent Protein Probes.
uml;k K Abstract We have developed probes based on the bacterial periplasmic glutamate/aspartate binding protein with either an endogenously fluorescent protein or a synthetic fluorophore as the indicator of glutamate binding for studying the kinetic mechanism of glutamate binding. iGluSnFR variants termed iGluh, iGlum, and iGlul cover a broad range of Kd-s (5.8 μM and 2.1 and 50 mM, respectively), and a novel fluorescently labeled indicator, Fl-GluBP, has a Kd of 9.7 μM. The fluorescence response kinetics of all the probes are consistent with a two-step mechanism involving ligand binding and isomerizat...
Source: Biophysical Journal - November 14, 2019 Category: Physics Authors: Coates C, Kerruth S, Helassa N, Török K Tags: Biophys J Source Type: research