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  • Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations
    Biophys. J. (IF 3.854) Pub Date : 2020-12-15
    Matthew D. McCoy; John Hamre; Dmitri K. Klimov; M. Saleet Jafri

    Distinct missense mutations in a specific gene have been associated with different diseases as well as differing severity of a disease. Current computational methods predict the potential pathogenicity of a missense variant but fail to differentiate between separate disease or severity phenotypes. We have developed a method to overcome this limitation by applying machine learning to features extracted

    更新日期:2021-01-19
  • Dynamics of Mechanically Coupled Hair-Cell Bundles of the Inner Ear
    Biophys. J. (IF 3.854) Pub Date : 2020-12-15
    Yuttana Roongthumskul; Justin Faber; Dolores Bozovic

    The high sensitivity and effective frequency discrimination of sound detection performed by the auditory system rely on the dynamics of a system of hair cells. In the inner ear, these acoustic receptors are primarily attached to an overlying structure that provides mechanical coupling between the hair bundles. Although the dynamics of individual hair bundles has been extensively investigated, the influence

    更新日期:2021-01-19
  • Mechanics of Bacterial Interaction and Death on Nanopatterned Surfaces
    Biophys. J. (IF 3.854) Pub Date : 2020-12-15
    Amar Velic; Jafar Hasan; Zhiyong Li; Prasad K.D.V. Yarlagadda

    Nanopatterned surfaces are believed to kill bacteria through physical deformation, a mechanism that has immense potential against biochemical resistance. Because of its elusive nature, this mechanism is mostly understood through biophysical modeling. Problematically, accurate descriptions of the contact mechanics and various boundary conditions involved in the bacteria-nanopattern interaction remain

    更新日期:2021-01-19
  • Mechanical Activation of MscL Revealed by a Locally Distributed Tension Molecular Dynamics Approach
    Biophys. J. (IF 3.854) Pub Date : 2020-12-15
    Rajitha Rajeshwar T.; Andriy Anishkin; Sergei Sukharev; Juan M. Vanegas

    Membrane tension perceived by mechanosensitive (MS) proteins mediates cellular responses to mechanical stimuli and osmotic stresses, and it also guides multiple biological functions including cardiovascular control and development. In bacteria, MS channels function as tension-activated pores limiting excessive turgor pressure, with MS channel of large conductance (MscL) acting as an emergency release

    更新日期:2021-01-19
  • Suppression of Lα/Lβ Phase Coexistence in the Lipids of Pulmonary Surfactant
    Biophys. J. (IF 3.854) Pub Date : 2020-12-19
    Jonathan R. Fritz; Ryan W. Loney; Stephen B. Hall; Stephanie Tristram-Nagle

    To determine how different constituents of pulmonary surfactant affect its phase behavior, we measured wide-angle x-ray scattering (WAXS) from oriented bilayers. Samples contained the nonpolar and phospholipids (N&PL) obtained from calf lung surfactant extract (CLSE), which also contains the hydrophobic surfactant proteins SP-B and SP-C. Mixtures with different ratios of N&PL and CLSE provided the

    更新日期:2021-01-19
  • Time-Resolved Fluorescence Anisotropy and Molecular Dynamics Analysis of a Novel GFP Homo-FRET Dimer
    Biophys. J. (IF 3.854) Pub Date : 2020-12-18
    Yurema Teijeiro-Gonzalez; Alessandro Crnjar; Andrew J. Beavil; Rebecca L. Beavil; Jakub Nedbal; Alix Le Marois; Carla Molteni; Klaus Suhling

    Förster resonance energy transfer (FRET) is a powerful tool to investigate the interaction between proteins in living cells. Fluorescence proteins, such as the green fluorescent protein (GFP) and its derivatives, are coexpressed in cells linked to proteins of interest. Time-resolved fluorescence anisotropy is a popular tool to study homo-FRET of fluorescent proteins as an indicator of dimerization

    更新日期:2021-01-19
  • Conformational Dynamics of Light-Harvesting Complex II in a Native Membrane Environment
    Biophys. J. (IF 3.854) Pub Date : 2020-12-05
    Fatemeh Azadi-Chegeni; Meaghan E. Ward; Giorgio Perin; Diana Simionato; Tomas Morosinotto; Marc Baldus; Anjali Pandit

    Photosynthetic light-harvesting complexes (LHCs) of higher plants, moss, and green algae can undergo dynamic conformational transitions, which have been correlated to their ability to adapt to fluctuations in the light environment. Herein, we demonstrate the application of solid-state NMR spectroscopy on native, heterogeneous thylakoid membranes of Chlamydomonas reinhardtii (Cr) and on Cr light-harvesting

    更新日期:2021-01-19
  • Multistep Changes in Amyloid Structure Induced by Cross-Seeding on a Rugged Energy Landscape
    Biophys. J. (IF 3.854) Pub Date : 2020-12-17
    Keisuke Yuzu; Naoki Yamamoto; Masahiro Noji; Masatomo So; Yuji Goto; Tetsushi Iwasaki; Motonari Tsubaki; Eri Chatani

    Amyloid fibrils are aberrant protein aggregates associated with various amyloidoses and neurodegenerative diseases. It is recently indicated that structural diversity of amyloid fibrils often results in different pathological phenotypes, including cytotoxicity and infectivity. The diverse structures are predicted to propagate by seed-dependent growth, which is one of the characteristic properties of

    更新日期:2021-01-19
  • Modeling of Hidden Structures Using Sparse Chemical Shift Data from NMR Relaxation Dispersion
    Biophys. J. (IF 3.854) Pub Date : 2020-12-08
    R. Bryn Fenwick; David Oyen; Henry van den Bedem; H. Jane Dyson; Peter E. Wright

    NMR relaxation dispersion measurements report on conformational changes occurring on the μs-ms timescale. Chemical shift information derived from relaxation dispersion can be used to generate structural models of weakly populated alternative conformational states. Current methods to obtain such models rely on determining the signs of chemical shift changes between the conformational states, which are

    更新日期:2021-01-19
  • Active and Inactive Cdc42 Differ in Their Insert Region Conformational Dynamics
    Biophys. J. (IF 3.854) Pub Date : 2020-12-19
    Nurit Haspel; Hyunbum Jang; Ruth Nussinov

    Cell division control protein 42 homolog (Cdc42) protein, a Ras superfamily GTPase, regulates cellular activities, including cancer progression. Using all-atom molecular dynamics (MD) simulations and essential dynamic analysis, we investigated the structure and dynamics of the catalytic domains of GDP-bound (inactive) and GTP-bound (active) Cdc42 in solution. We discovered substantial differences in

    更新日期:2021-01-19
  • Circadian Rhythms of Early Afterdepolarizations and Ventricular Arrhythmias in a Cardiomyocyte Model
    Biophys. J. (IF 3.854) Pub Date : 2020-12-05
    Casey O. Diekman; Ning Wei

    Sudden cardiac arrest is a malfunction of the heart’s electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events

    更新日期:2021-01-19
  • Modeling Thrombus Shell: Linking Adhesion Receptor Properties and Macroscopic Dynamics
    Biophys. J. (IF 3.854) Pub Date : 2021-01-19
    Valeriia N. Kaneva; Joanne L. Dunster; Vitaly Volpert; Fazoil Ataullahanov; Mikhail A. Panteleev; Dmitry Yu Nechipurenko

    Damage to arterial vessel walls leads to the formation of platelet aggregate, which acts as a physical obstacle for bleeding. An arterial thrombus is heterogeneous; it has a dense inner part (core) and an unstable outer part (shell). The thrombus shell is very dynamic, being composed of loosely connected discoid platelets. The mechanisms underlying the observed mobility of the shell and its (patho)physiological

    更新日期:2021-01-19
  • Mechanisms of Premature Ventricular Complexes Caused by QT Prolongation
    Biophys. J. (IF 3.854) Pub Date : 2020-12-15
    Zhaoyang Zhang; Michael B. Liu; Xiaodong Huang; Zhen Song; Zhilin Qu

    QT prolongation, due to lengthening of the action potential duration in the ventricles, is a major risk factor of lethal ventricular arrhythmias. A widely known consequence of QT prolongation is the genesis of early afterdepolarizations (EADs), which are associated with arrhythmias through the generation of premature ventricular complexes (PVCs). However, the vast majority of the EADs observed experimentally

    更新日期:2021-01-19
  • Impact of Self-Association on the Architectural Properties of Bacterial Nucleoid Proteins
    Biophys. J. (IF 3.854) Pub Date : 2020-12-17
    Marc Joyeux

    The chromosomal DNA of bacteria is folded into a compact body called the nucleoid, which is composed essentially of DNA (∼80%), RNA (∼10%), and a number of different proteins (∼10%). These nucleoid proteins act as regulators of gene expression and influence the organization of the nucleoid by bridging, bending, or wrapping the DNA. These so-called architectural properties of nucleoid proteins are still

    更新日期:2021-01-19
  • Intrinsic Disorder in the T Cell Receptor Creates Cooperativity and Controls ZAP70 Binding
    Biophys. J. (IF 3.854) Pub Date : 2020-12-05
    Lara Clemens; Omer Dushek; Jun Allard

    Many immunoreceptors have cytoplasmic domains that are intrinsically disordered (i.e., have high configurational entropy), have multiple sites of posttranslational modification (e.g., tyrosine phosphorylation), and participate in nonlinear signaling pathways (e.g., exhibiting switch-like behavior). Several hypotheses to explain the origin of these nonlinearities fall under the broad hypothesis that

    更新日期:2021-01-19
  • Refinement of a Cryo-EM Structure of hERG: Bridging Structure and Function
    Biophys. J. (IF 3.854) Pub Date : 2021-01-19
    Hanif M. Khan; Jiqing Guo; Henry J. Duff; D. Peter Tieleman; Sergei Y. Noskov

    The human ether-a-go-go-related gene (hERG) encodes the voltage gated potassium channel (KCNH2 or Kv11.1, commonly known as hERG). This channel plays a pivotal role in the stability of phase 3 repolarization of the cardiac action potential. Although a high-resolution cryo-EM structure is available for its depolarized (open) state, the structure surprisingly did not feature many functionally important

    更新日期:2021-01-19
  • 2.5Å-resolution structure of the human CDK-activating kinase bound to the clinical inhibitor ICEC0942
    Biophys. J. (IF 3.854) Pub Date : 2021-01-19
    Basil J. Greber; Jonathan Remis; Simak Ali; Eva Nogales

    The human CDK-activating kinase (CAK), composed of CDK7, cyclin H, and MAT1, is involved in the control of transcription initiation and the cell cycle. Due to these activities, it has been identified as a promising target for cancer chemotherapy. A number of CDK7 inhibitors have entered clinical trials, among them ICEC0942 (also known as CT7001). Structural information can aid to improve the affinity

    更新日期:2021-01-19
  • Recurrent Dynamics of Rupture Transitions of Giant Lipid Vesicles at Solid Surfaces
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Viviane N. Ngassam; Wan-Chih Su; Douglas L. Gettel; Yawen Deng; Zexu Yang; Neven Wang-Tomic; Varun P. Sharma; Sowmya Purushothaman; Atul N. Parikh

    Single giant unilamellar vesicles (GUVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophobic surfaces, the GUVs rupture via a recurrent, bouncing ball rhythm. During each contact, the GUVs, rendered tense by the substrate interactions, porate and spread a molecularly transformed motif of a monomolecular layer on the hydrophobic surface from the point of contact

    更新日期:2021-01-18
  • Influence of membrane-cortex linkers on the extrusion of membrane tubes
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Alexandru Paraschiv; Thibaut J. Lagny; Christian Vanhille Campos; Evelyne Coudrier; Patricia Bassereau; Anela Šarić

    The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here we investigate the role of membrane-cortex linkers

    更新日期:2021-01-18
  • Improving SARS-CoV-2 Structures: Peer Review by Early Coordinate Release
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Tristan I. Croll; Christopher J. Williams; Vincent B. Chen; David C. Richardson; Jane S. Richardson

    This work builds upon the record-breaking speed and generous immediate release of new experimental 3D structures of the SARS-CoV-2 proteins and complexes, which are crucial to downstream vaccine and drug development. We have surveyed those structures to catch the occasional errors that could be significant for those important uses and for which we were able to provide demonstrably higher-accuracy corrections

    更新日期:2021-01-18
  • Topological Polymorphism of Nucleosome Fibers and Folding of Chromatin
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Victor B. Zhurkin; Davood Norouzi

    We discuss recent observations of polymorphic chromatin packaging at the oligo-nucleosomal level and compare them with computer simulations. Our computations reveal two topologically different families of two-start 30-nm fiber conformations distinguished by the linker length, L: fibers with L ≈ 10n and L ≈ 10n+5 bp have DNA linking numbers per nucleosome of ΔLk ≈ –1.5 and –1.0, respectively (where

    更新日期:2021-01-18
  • Fat Inclusions Strongly Alter Membrane Mechanics.
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Alexandre Santinho; Aymeric Chorlay; Lionel Foret; Abdou Rachid Thiam

    Neutral lipids (NLs) are apolar oil molecules synthesized in the endoplasmic reticulum (ER) bilayer upon diverse biological stimuli. NLs synthesized are released in the hydrophobic core of the bilayer. At a critical concentration, NLs condense by phase separation and nucleate a lipid droplet (LD). After an LD forms, a fraction of NLs can be present in the bilayer but at a concentration below that of

    更新日期:2021-01-18
  • Mechanics of a molecular mousetrap-- nucleation-limited innate immune signaling
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Alejandro Rodríguez Gama; Tayla Miller; Randal Halfmann

    Innate immune responses, such as cell death and inflammatory signaling, are typically switch-like in nature. They also involve “prion-like” self-templating polymerization of one or more signaling proteins into massive macromolecular assemblies known as signalosomes. Despite the wealth of atomic-resolution structural information on signalosomes, how the constituent polymers nucleate, and whether the

    更新日期:2021-01-18
  • pH-triggered pore-forming peptides with strong composition-dependent membrane selectivity
    Biophys. J. (IF 3.854) Pub Date : 2021-01-16
    Sarah Y. Kim; Ana-Nicoleta Bondar; William C. Wimley; Kalina Hristova

    Peptides that self-assemble into nanometer-sized pores in lipid bilayers could have utility in a variety of biotechnological and clinical applications if we can understand their physical chemical properties and learn to control their membrane selectivity. To empower such control, we have used synthetic molecular evolution to identify the pHD peptides, a family of peptides that assemble into macromolecule-sized

    更新日期:2021-01-18
  • Fundamentals of the logarithmic measure for revealing multimodal diffusion
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Benjamin A. Dalton; Ivo F. Sbalzarini; Itsuo Hanasaki

    We develop a theoretical foundation for a time-series analysis method suitable for revealing the spectrum of diffusion coefficients in mixed Brownian systems, where no prior knowledge of particle distinction is required. This method is directly relevant for particle tracking in biological systems, where diffusion processes are often non-uniform. We transform Brownian data onto the logarithmic domain

    更新日期:2021-01-14
  • Intestinal Villus Structure Contributes to Even Shedding of Epithelial Cells
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Yuto Kai

    In the intestinal epithelium, proliferated epithelial cells ascend the crypts and villi and shed at the villus tips into the gut lumen. In this study, we theoretically investigate the roles of the villi on cell turnover. We present a stochastic model that focuses on the duration over which cells migrate the shortest paths between the crypt orifices and the villus tips, where shedding cells are randomly

    更新日期:2021-01-14
  • Quantifying Viscosity and Surface Tension of Multi-Component Protein-Nucleic Acid Condensates
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Ibraheem Alshareedah; George M. Thurston; Priya R. Banerjee

    Living cells organize their internal space into dynamic condensates through liquid-liquid phase separation of multivalent proteins in association with cellular nucleic acids. Here we study how variations in nucleic acid (NA)-to-protein stoichiometry modulate the condensed phase organization and fluid dynamics in a model system of multi-component heterotypic condensates. Employing a multi-parametric

    更新日期:2021-01-14
  • Trajectory-based energy landscapes of gene regulatory networks
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Harish Venkatachalapathy; Samira M. Azarin; Casim A. Sarkar

    Multistability and natural biological variability can result in significant heterogeneity within a cell population, leading to challenges in understanding and modulating cell behavior. Energy landscapes can offer qualitatively intuitive visualizations of cell phenotype and facilitate a more quantitative understanding of cellular dynamics, but current methods for landscape generation are mathematically

    更新日期:2021-01-14
  • Vitamin B12-peptide nucleic acids use the BtuB receptor to pass through the E. coli outer membrane
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Tomasz Pienko; Jakub Czarnecki; Marcin Równicki; Monika Wojciechowska; Aleksandra J. Wierzba; Dorota Gryko; Dariusz Bartosik; Joanna Trylska

    Short modified oligonucleotides that bind in a sequence-specific way to mRNA essential for bacterial growth could be useful to fight bacterial infections. One such promising oligonucleotide is peptide nucleic acid (PNA), a synthetic DNA analog with a peptide-like backbone. However, the limitation precluding the use of oligonucleotides, including PNA, is that bacteria do not import them from the environment

    更新日期:2021-01-14
  • Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Jekabs Krigerts; Kristine Salmina; Talivaldis Freivalds; Pawel Zayakin; Felikss Rumnieks; Inna Inashkina; Alessandro Giuliani; Michael Hausmann; Jekaterina Erenpreisa

    Finding out how cells prepare for fate change during differentiation commitment was our task. To address if the constitutive pericentromere associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is used in the therapy of cancer. PAD-repressive heterochromatin

    更新日期:2021-01-14
  • Short Peptides as Predictors for the Structure of Polyarginine Sequences in Disordered Proteins
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    B. Milorey; R. Schweitzer-Stenner; B. Andrews; H. Schwalbe; B. Urbanc

    Intrinsically disordered proteins (IDPs) and regions (IDRs) are frequently enriched in charged amino acids. IDRs are regularly involved in important biological processes, where one or more charged residues is the driving force behind a protein-biomolecule interaction. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges have a high

    更新日期:2021-01-14
  • SNARE Complex Alters the Interactions of the Ca2+ sensor Synaptotagmin 1 with Lipid Bilayers
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Maria Bykhovskaia

    Release of neuronal transmitters from nerve terminals is triggered by the molecular Ca2+ sensor Synaptotagmin 1 (Syt1). Syt1 is a transmembrane protein attached to the synaptic vesicle (SV), and its cytosolic region comprises two domains, C2A and C2B, which are thought to penetrate into lipid bilayers upon Ca2+ binding. Prior to fusion, SVs become attached to the presynaptic membrane (PM) by the four-helical

    更新日期:2021-01-14
  • High throughput mechanobiology: Force modulation of ensemble biochemical and cell-based assays
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Ália dos Santos; Natalia Fili; David S. Pearson; Yukti Hari-Gupta; Christopher P. Toseland

    Mechanobiology is focused on how the physical forces and mechanical properties of proteins, cells and tissues contribute to physiology and disease. While the response of proteins and cells to mechanical stimuli is critical for function, the tools to probe these activities are typically restricted to single molecule manipulations. Here, we have developed a novel microplate reader assay to encompass

    更新日期:2021-01-14
  • Unfolding of the chromatin fiber driven by overexpression of non-interacting bridging factors
    Biophys. J. (IF 3.854) Pub Date : 2021-01-14
    Isha Malhotra; Bernardo Oyarzun; Bortolo Matteo Mognetti

    Nuclear molecules control the functional properties of the chromatin fiber by shaping its morphological properties. The biophysical mechanisms controlling how bridging molecules compactify chromatin are a matter of debate. On the one side, bridging molecules could cross-link faraway sites and fold the fiber through the formation of loops. Interacting bridging molecules could also mediate long-range

    更新日期:2021-01-14
  • Lingering Dynamics in Microvascular Blood Flow
    Biophys. J. (IF 3.854) Pub Date : 2021-01-12
    Alexander Kihm; Stephan Quint; Matthias W. Laschke; Michael D. Menger; Thomas John; Lars Kaestner; Christian Wagner

    The microvascular networks in the body of vertebrates consist of the smallest vessels such as arterioles, capillaries, and venules. The flow of red blood cells (RBCs) through these networks ensures the gas exchange in as well as the transport of nutrients to the tissues. Any alterations in this blood flow may have severe implications on the health state. Because the vessels in these networks obey dimensions

    更新日期:2021-01-12
  • Quantifying Intracellular Particle Flows by DIC Object Tracking
    Biophys. J. (IF 3.854) Pub Date : 2021-01-11
    Anushree R. Chaphalkar; Yash K. Jawale; Dhruv Khatri; Chaitanya A. Athale

    Label-free imaging techniques such as differential interference contrast (DIC) allow the observation of cells and large subcellular structures in their native, unperturbed states with minimal exposure to light. The development of robust computational image-analysis routines is vital to quantitative label-free imaging. The reliability of quantitative analysis of time-series microscopy data based on

    更新日期:2021-01-11
  • Generalizing HMMs to Continuous Time for Fast Kinetics: Hidden Markov Jump Processes
    Biophys. J. (IF 3.854) Pub Date : 2021-01-07
    Zeliha Kilic; Ioannis Sgouralis; Steve Pressé

    The hidden Markov model (HMM) is a framework for time series analysis widely applied to single molecule experiments. Although initially developed for applications outside the Natural Sciences, the HMM has traditionally been used to interpret signals generated by physical systems, such as single molecules, evolving in a discrete state space observed at discrete time levels dictated by the data acquisition

    更新日期:2021-01-07
  • Correlative imaging of motoneuronal cell elasticity by pump and probe spectroscopy
    Biophys. J. (IF 3.854) Pub Date : 2021-01-07
    Ahmed Hamraoui; Océane Sénépart; Maxime Schneider; Sophie Malaquin; Emmanuel Péronne; Loïc Becerra; Fannie Semprez; Claire Legay; Laurent Belliard

    Because of their role of information transmitter between the spinal cord and the muscle fibers, motor neurons are subject to physical stimulation and mechanical properties modifications. We report on motoneuron elasticity investigated by time resolved pump and probe spectroscopy. A dual picosecond geometry probing simultaneously the acoustic impedance mismatch at the cell/Titanium transducer interface

    更新日期:2021-01-07
  • Particle Diffusivity and Free-Energy Profiles in Hydrogels from Time-Resolved Penetration Data
    Biophys. J. (IF 3.854) Pub Date : 2021-01-07
    Amanuel Wolde-Kidan; Anna Herrmann; Albert Prause; Michael Gradzielski; Rainer Haag; Stephan Block; Roland R. Netz

    A combined experimental/theoretical method to simultaneously determine diffusivity and free-energy profiles of particles that penetrate into inhomogeneous hydrogel systems is presented. As the only input, arbitrarily normalized concentration profiles from fluorescence intensity data of labeled tracer particles for different penetration times are needed. The method is applied to dextran molecules of

    更新日期:2021-01-07
  • Angular precision of radical pair compass magnetoreceptors
    Biophys. J. (IF 3.854) Pub Date : 2021-01-07
    Yi Ren; Hamish G. Hiscock; P.J. Hore

    The light-dependent magnetic compass sense of night-migratory songbirds is thought to rely on magnetically sensitive chemical reactions of radical pairs in cryptochrome proteins located in the birds’ eyes. Recently Hiscock et al. (Q. Rev. Biophys. 52 (2019) e9, 1-10) developed an information theory approach to obtain a strict lower bound on the precision with which a bird could estimate its head direction

    更新日期:2021-01-07
  • Hsp70 inhibits aggregation of Islet amyloid polypeptide by binding to the heterogeneous prenucleation oligomers
    Biophys. J. (IF 3.854) Pub Date : 2021-01-06
    Neeraja Chilukoti; Timir Baran Sil; Bankanidhi Sahoo; S. Deepa; Sreelakshmi Cherakara; Mithun Maddheshiya; Kanchan Garai

    Molecular chaperone Hsp70 plays important roles in the pathology of amyloid diseases by inhibiting aberrant aggregation of proteins. However, biophysical mechanism of the interaction of Hsp70 with the intrinsically disordered proteins (IDPs) is unclear. Here, we report that Hsp70 inhibits aggregation of Islet amyloid polypeptide (IAPP) at substoichiometric concentrations under diverse solutions conditions

    更新日期:2021-01-06
  • Troponin Revealed: Uncovering the Structure of the Thin Filament On-Off Switch in Striated Muscle
    Biophys. J. (IF 3.854) Pub Date : 2020-11-20
    Larry S. Tobacman

    Recently, our understanding of the structural basis of troponin-tropomyosin’s Ca2+-triggered regulation of striated muscle contraction has advanced greatly, particularly via cryo-electron microscopy data. Compelling atomic models of troponin-tropomyosin-actin were published for both apo- and Ca2+-saturated states of the cardiac thin filament. Subsequent electron microscopy and computational analyses

    更新日期:2021-01-05
  • Computational Tool for Ensemble Averaging of Single-Molecule Data
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Thomas Blackwell; W. Tom Stump; Sarah R. Clippinger; Michael J. Greenberg

    Molecular motors couple chemical transitions to conformational changes that perform mechanical work in a wide variety of biological processes. Disruption of this coupling can lead to diseases, and therefore there is a need to accurately measure mechanochemical coupling in motors in both health and disease. Optical tweezers with nanometer spatial and millisecond temporal resolution have provided valuable

    更新日期:2021-01-05
  • Sample Preparation and Imaging Conditions Affect mEos3.2 Photophysics in Fission Yeast Cells
    Biophys. J. (IF 3.854) Pub Date : 2020-11-18
    Mengyuan Sun; Kevin Hu; Joerg Bewersdorf; Thomas D. Pollard

    Photoconvertible fluorescent proteins (PCFPs) are widely used in super-resolution microscopy and studies of cellular dynamics. However, our understanding of their photophysics is still limited, hampering their quantitative application. For example, we do not know the optimal sample preparation methods or imaging conditions to count protein molecules fused to PCFPs by single-molecule localization microscopy

    更新日期:2021-01-05
  • Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Anna H. Lippert; Ivan B. Dimov; Alexander K. Winkel; Jane Humphrey; James McColl; Kevin Y. Chen; Ana M. Santos; Edward Jenkins; Kristian Franze; Simon J. Davis; David Klenerman

    Much of what we know about the early stages of T cell activation has been obtained from studies of T cells interacting with glass-supported lipid bilayers that favor imaging but are orders of magnitude stiffer than typical cells. We developed a method for attaching lipid bilayers to polydimethylsiloxane polymer supports, producing “soft bilayers” with physiological levels of mechanical resistance (Young’s

    更新日期:2021-01-05
  • Lipid-Composition-Mediated Forces Can Stabilize Tubular Assemblies of I-BAR Proteins
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Zack Jarin; Alexander J. Pak; Patricia Bassereau; Gregory A. Voth

    Collective action by inverse-Bin/Amphiphysin/Rvs (I-BAR) domains drive micron-scale membrane remodeling. The macroscopic curvature sensing and generation behavior of I-BAR domains is well characterized, and computational models have suggested various mechanisms on simplified membrane systems, but there remain missing connections between the complex environment of the cell and the models proposed thus

    更新日期:2021-01-05
  • The Biased Ligands NGF and NT-3 Differentially Stabilize Trk-A Dimers
    Biophys. J. (IF 3.854) Pub Date : 2020-12-05
    Fozia Ahmed; Elmer Zapata-Mercado; Sanim Rahman; Kalina Hristova

    Trk-A is a receptor tyrosine kinase (RTK) that plays an essential role in the development and functioning of the nervous system. Trk-A is expressed in neurons and signals in response to two ligands, NGF and neurotrophin-3 (NT-3), with very different functional consequences. Thus, NGF and NT-3 are “biased” ligands for Trk-A. Because it has been hypothesized that biased RTK ligands induce differential

    更新日期:2021-01-05
  • Molecular Dynamics Study of Structure, Folding, and Aggregation of Poly-PR and Poly-GR Proteins
    Biophys. J. (IF 3.854) Pub Date : 2020-11-28
    Size Zheng; Ali Sahimi; Katherine S. Shing; Muhammad Sahimi

    Poly-proline-arginine (poly-PR) and poly-glycine-arginine (poly-GR) proteins are believed to be the most toxic dipeptide repeat (DPR) proteins that are expressed by the hexanucleotide repeat expansion mutation in C9ORF72, which are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) diseases. Their structural information and mechanisms of toxicity remain incomplete

    更新日期:2021-01-05
  • Potassium Glutamate and Glycine Betaine Induce Self-Assembly of the PCNA and β-Sliding Clamps
    Biophys. J. (IF 3.854) Pub Date : 2020-11-19
    Anirban Purohit; Lauren G. Douma; Linda B. Bloom; Marcia Levitus

    Sliding clamps are oligomeric ring-shaped proteins that increase the efficiency of DNA replication. The stability of the Escherichia coli β-clamp, a homodimer, is particularly remarkable. The dissociation equilibrium constant of the β-clamp is of the order of 10 pM in buffers of moderate ionic strength. Coulombic electrostatic interactions have been shown to contribute to this remarkable stability

    更新日期:2021-01-05
  • Fibrillation of Human Calcitonin and Its Analogs: Effects of Phosphorylation and Disulfide Reduction
    Biophys. J. (IF 3.854) Pub Date : 2020-11-18
    Harshil K. Renawala; Karthik B. Chandrababu; Elizabeth M. Topp

    Some therapeutic peptides self-assemble in solution to form ordered, insoluble, β-sheet-rich amyloid fibrils. This physical instability can result in reduced potency, cause immunogenic side effects, and limit options for formulation. Understanding the mechanisms of fibrillation is key to developing rational mitigation strategies. Here, amide hydrogen-deuterium exchange with mass spectrometric analysis

    更新日期:2021-01-05
  • Targeting Telomeres: Molecular Dynamics and Free Energy Simulation of Gold-Carbene Binding to DNA
    Biophys. J. (IF 3.854) Pub Date : 2020-12-05
    Asmar Nayis; Korbinian Liebl; Christina V. Frost; Martin Zacharias

    DNA sequences in regulatory regions and in telomers at the ends of chromosomes frequently contain tandem repeats of guanine nucleotides that can form stacked structures stabilized by Hoogsten pairing and centrally bound monovalent cations. The replication and elongation of telomeres requires the disruption of these G-quadruplex structures. Hence, drug molecules such as gold (Au)-carbene that stabilize

    更新日期:2021-01-05
  • A Simulation Study of the Role of Mechanical Stretch in Arrhythmogenesis during Cardiac Alternans
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Azzam Hazim; Youssef Belhamadia; Stevan Dubljevic

    The deformation of the heart tissue due to the contraction can modulate the excitation, a phenomenon referred to as mechanoelectrical feedback (MEF), via stretch-activated channels. The effects of MEF on the electrophysiology at high pacing rates are shown to be proarrhythmic in general. However, more studies need to be done to elucidate the underlying mechanism. In this work, we investigate the effects

    更新日期:2021-01-05
  • Kinetic Membrane Model of Outer Hair Cells
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Kuni H. Iwasa

    The effectiveness of outer hair cells (OHCs) in amplifying the motion of the organ of Corti, and thereby contributing to the sensitivity of mammalian hearing, depends on the mechanical power output of these cells. Electromechanical coupling in OHCs, which enables these cells to convert electrical energy into mechanical energy, has been analyzed in detail using isolated cells using primarily static

    更新日期:2021-01-05
  • Persistence as an Optimal Hedging Strategy
    Biophys. J. (IF 3.854) Pub Date : 2020-11-28
    Alexander P. Browning; Jesse A. Sharp; Tarunendu Mapder; Christopher M. Baker; Kevin Burrage; Matthew J. Simpson

    Bacteria invest in a slow-growing subpopulation, called persisters, to ensure survival in the face of uncertainty. This hedging strategy is remarkably similar to financial hedging, where diversifying an investment portfolio protects against economic uncertainty. We provide a new, to our knowledge, theoretical foundation for understanding cellular hedging by unifying the study of biological population

    更新日期:2021-01-05
  • Conformational Ensembles of Antibodies Determine Their Hydrophobicity
    Biophys. J. (IF 3.854) Pub Date : 2020-11-18
    Franz Waibl; Monica L. Fernández-Quintero; Anna S. Kamenik; Johannes Kraml; Florian Hofer; Hubert Kettenberger; Guy Georges; Klaus R. Liedl

    A major challenge in the development of antibody biotherapeutics is their tendency to aggregate. One root cause for aggregation is exposure of hydrophobic surface regions to the solvent. Many current techniques predict the relative aggregation propensity of antibodies via precalculated scales for the hydrophobicity or aggregation propensity of single amino acids. However, those scales cannot describe

    更新日期:2021-01-05
  • Membrane-Mediated Ligand Unbinding of the PK-11195 Ligand from TSPO
    Biophys. J. (IF 3.854) Pub Date : 2020-11-20
    Tom Dixon; Arzu Uyar; Shelagh Ferguson-Miller; Alex Dickson

    The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is of longstanding medical interest as both a biomarker for neuroinjury and a potential drug target for neuroinflammation and other disorders. Recently, it was shown that ligand residence time is a key factor determining steroidogenic efficacy of TSPO-binding compounds. This spurs interest in simulations of

    更新日期:2021-01-05
  • Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels
    Biophys. J. (IF 3.854) Pub Date : 2020-11-26
    Kelly L. McGuire; Phillip Smit; Daniel H. Ess; Jonathan T. Hill; Roger G. Harrison; David D. Busath

    Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block

    更新日期:2021-01-05
  • Nonlinear mechanical properties of prestressed branched fibrous networks
    Biophys. J. (IF 3.854) Pub Date : 2021-01-05
    Hamed Hatami-Marbini; Milad Rohanifar

    Random fiber networks constitute the solid skeleton of many biological materials such as the cytoskeleton of cells and extracellular matrix of soft tissues. These random networks show unique mechanical properties such as nonlinear shear strain stiffening and strain softening when subjected to preextension and precompression, respectively. In the present study, we perform numerical simulations in order

    更新日期:2021-01-05
  • Resolving Cargo-motor-track Interactions in Living Cells with Bifocal Parallax Single Particle Tracking
    Biophys. J. (IF 3.854) Pub Date : 2020-12-25
    Xiaodong Cheng; Kuangcai Chen; Bin Dong; Seth L. Filbrun; Gufeng Wang; Ning Fang

    Resolving coordinated biomolecular interactions in living cellular environments is vital for understanding the mechanisms of molecular nanomachines. The conventional approach relies on localizing and tracking target biomolecules and/or subcellular organelles labeled with imaging probes. However, it is challenging to gain information on rotational dynamics, which can be more indicative of the work done

    更新日期:2020-12-25
  • 2 ns electrostimulation of Ca2+ influx into chromaffin cells: rapid modulation by field reversal
    Biophys. J. (IF 3.854) Pub Date : 2020-12-25
    Josette Zaklit; Gale L. Craviso; Normand Leblanc; P. Thomas Vernier; Esin B. Sözer

    Cellular effects of nanosecond pulsed electric field exposures can be attenuated by an electric field reversal, a phenomenon called bipolar pulse cancellation. Our investigations of this phenomenon in neuroendocrine adrenal chromaffin cells show that a single 2 ns, 16 MV/m unipolar pulse elicited a rapid, transient rise in intracellular Ca2+ levels due to Ca2+ influx through voltage-gated calcium channels

    更新日期:2020-12-25
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