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Understanding the Free Energy Landscape of Phase Separation in Lipid Bilayers using Molecular Dynamics Biophys. J. (IF 3.4) Pub Date : 2023-09-23 Ashlin J. Poruthoor, Akshara Sharma, Alan Grossfield
Liquid-liquid phase separation (LLPS) inside the cell often results in biological condensates that can critically impact cell homeostasis. Such phase separation events occur in multiple parts of cells, including the cell membranes, where the so-called “lipid raft” hypothesis posits the formation of ordered domains floating in a sea of disordered lipids. The resulting lipid domains often have functional
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Simulations suggest a scaffolding mechanism of membrane deformation by the caveolin 8S complex Biophys. J. (IF 3.4) Pub Date : 2023-09-22 Sayyid Yobhel Vasquez Rodriguez, Themis Lazaridis
Caveolins form complexes of various sizes that deform membranes into polyhedral shapes. However, the recent structure of the 8S complex was disk-like with a flat membrane-binding surface. How can a flat complex deform membranes into nonplanar structures? Molecular dynamics simulations revealed that the 8S complex rapidly takes the form of a suction cup. Simulations on implicit membrane vesicles determined
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Cholesterol catalyzes unfolding in membrane inserted motifs of the pore forming protein cytolysin A Biophys. J. (IF 3.4) Pub Date : 2023-09-22 Avijeet Kulshrestha, Sudeep N. Punnathanam, Rahul Roy, K. Ganapathy Ayappa
Plasma membrane induced protein folding and conformational transitions play a central role in cellular homeostasis. Several transmembrane proteins are folded in the complex lipid milieu to acquire a specific structure and function. Bacterial pore forming toxins (PFTs) are proteins expressed by a large class of pathogenic bacteria that exploit the plasma membrane environment to efficiently undergo secondary
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Utility of FRET in studies of membrane protein oligomerization: the concept of the effective dissociation constant Biophys. J. (IF 3.4) Pub Date : 2023-09-21 Daniel McKenzie, Daniel Wirth, Taras V. Pogorelov, Kalina Hristova
The activity of many membrane receptors is controlled through their lateral association into dimers or higher order oligomers. While Förster resonance energy transfer (FRET) measurements have been used extensively to characterize the stability of receptor dimers, the utility of FRET in studies of larger oligomers has been limited. Here we introduce an effective equilibrium dissociation constant that
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Crystal Structures of Human Serum Albumin in Complex with Lysophosphatidylcholine Biophys. J. (IF 3.4) Pub Date : 2023-09-19 Yu Wang, Zhipu Luo, Xavier Morelli, Peng Xu, Longguang Jiang, Xiaoli Shi, Mingdong Huang
Lysophospholipids (lysoPLs) are crucial metabolites involved in various physiological and pathological cellular processes. Understanding their binding interactions, particularly with human serum albumin (HSA), is essential due to their role in regulating lysoPLs-induced cytotoxicity. However, the precise mechanism of lysoPLs binding to HSA remains elusive. In this study, we employed fluorescence quenching
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Fluorophore position of headgroup-labeled Gb3 glycosphingolipids in lipid bilayers Biophys. J. (IF 3.4) Pub Date : 2023-09-21 Larissa Socrier, Akshita Sharma, Tao Chen, Kira Flato, Katharina Kettelhoit, Jörg Enderlein, Daniel B. Werz, Claudia Steinem
Fluorescent lipid probes are an invaluable tool for investigating lipid membranes. In particular, localizing particular receptor lipids such as glycosphingolipids within phase-separated membranes is of pivotal interest to understanding the influence of protein-receptor lipid binding on membrane organization. However, fluorescent labeling can readily alter the phase behavior of a lipid membrane because
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Structure adaptation in Omicron SARS-CoV-2/hACE2: Biophysical origins of evolutionary driving forces Biophys. J. (IF 3.4) Pub Date : 2023-09-16 Ya-Wen Hsiao, David J. Bray, Tseden Taddese, Guadalupe Jiménez-Serratos, Jason Crain
Since its emergence, the COVID-19 threat has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the
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Crowder titrations enable the quantification of driving forces for macromolecular phase separation Biophys. J. (IF 3.4) Pub Date : 2023-09-16 Gaurav Chauhan, Anne Bremer, Furqan Dar, Tanja Mittag, Rohit V. Pappu
Macromolecular solubility is an important contributor to the driving forces for phase separation. Formally, the driving forces in a binary mixture comprising a macromolecule dissolved in a solvent can be quantified in terms of the saturation concentration, which is the threshold macromolecular concentration above which the mixture separates into coexisting dense and dilute phases. Additionally, the
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The physical landscape of CAR-T synapse Biophys. J. (IF 3.4) Pub Date : 2023-09-15 Yiwei Xiong, Kendra A. Libby, Xiaolei Su
Chimeric antigen receptor (CAR)-T cells form dynamic immunological synapses with their cancer cell targets. Following a CAR-antigen engagement, the CAR-T synapse forms, matures, and finally disassembles, accompanied by substantial remodeling of cell surface proteins, lipids, and glycans. In this review, we provide perspectives for understanding protein distribution, membrane topology, and force transmission
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Estimating the Probability of Early Afterdepolarizations and Predicting Arrhythmic Risk associated with Long QT Syndrome Type 1 Mutations Biophys. J. (IF 3.4) Pub Date : 2023-09-12 Qingchu Jin, Joseph L. Greenstein, Raimond L. Winslow
Early after-depolarizations (EADs) are action potential (AP) repolarization abnormalities that can trigger lethal arrhythmias. Simulations using biophysically-detailed cardiac myocyte models can reveal how model parameters influence the probability of these cellular arrhythmias, however such analyses can pose a huge computational burden. We have previously developed a highly simplified approach in
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Subunit-specific inhibition of BK channels by piperine Biophys. J. (IF 3.4) Pub Date : 2023-09-12 Aravind Kshatri, Belinda Rivero-Pérez, Teresa Giraldez
Piperine is the principal alkaloid present in black pepper and is well-known for its diverse pharmacological effects, including inhibition of different ion channels. Large conductance Ca2+-activated K+ channels (BK) are widely expressed across several tissues and play a vital role in many physiological functions. In this study, we have investigated the pharmacological effects of piperine on various
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Who wants yesterday’s papers? Biophys. J. (IF 3.4) Pub Date : 2023-09-05 Heiko Heerklotz
Abstract not available
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Stochastic modeling of the mRNA life process: A generalized master equation Biophys. J. (IF 3.4) Pub Date : 2023-08-30 Changhong Shi, Xiyan Yang, Jiajun Zhang, Tianshou Zhou
The mRNA life cycle is a complex biochemical process, involving transcription initiation, elongation, termination, splicing, and degradation. Each of these molecular events is multistep and can create a memory. The effect of this molecular memory on gene expression is not clear although there are many related yet scattered experimental reports. To address this important issue, we develop a general
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Vesicle Budding caused by Lysolipid-Induced Asymmetry Stress Biophys. J. (IF 3.4) Pub Date : 2023-08-29 Lisa Hua, Michael Kaiser, Iulia Carabadjac, Annette Meister, Gerd Hause, Heiko Heerklotz
Lysolipids such as lauroyl, myristoyl and palmitoyl lysophosphatidylcholine (LPC) insert into the outer leaflet of liposomes but do not flip to the inner leaflet over many hours. This way, they create asymmetry stress between the intrinsic areas of the two leaflets. We have studied how this stress is relaxed with particular emphasis on the budding and fission of small (diameter 20 – 30 nm) daughter
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Three membrane fusion pore families determine the pathway to pore dilation Biophys. J. (IF 3.4) Pub Date : 2023-08-28 Rui Su, Shuyuan Wang, Zachary McDargh, Ben O’Shaughnessy
During exocytosis secretory vesicles fuse with a target membrane and release neurotransmitters, hormones or other bioactive molecules through a membrane fusion pore. The initially small pore may subsequently dilate for full contents release, as commonly observed in amperometric traces. The size, shape and evolution of the pore is critical to the course of contents release, but exact fusion pore solutions
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Native and non-native reactions in ethanolamine ammonia-lyase are actuated by different dynamics Biophys. J. (IF 3.4) Pub Date : 2023-08-28 Wei Li, Kurt Warncke
We address the contribution of select classes of solvent-coupled configurational fluctuations to the complex choreography involved in configurational and chemical steps in an enzyme by comparing native and non-native reactions conducted at different protein-internal sites. The low-temperature, first-order kinetics of covalent bond rearrangement of the cryotrapped substrate radical in coenzyme B12-dependent
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Celebrating the creative scientific life of Ken Jacobson Biophys. J. (IF 3.4) Pub Date : 2023-08-28 Klaus M. Hahn, Michelle S. Itano, Leslie M. Loew, Eric A. Vitriol
Abstract not available
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G-actin diffusion is insufficient to achieve F-actin assembly in fast-treadmilling protrusions Biophys. J. (IF 3.4) Pub Date : 2023-08-28 Ravikanth Appalabhotla, Mitchell T. Butler, James E. Bear, Jason M. Haugh
To generate forces that drive migration of a eukaryotic cell, arrays of actin filaments (F-actin) are assembled at the cell’s leading membrane edge. To maintain cell propulsion and respond to dynamic external cues, actin filaments must be disassembled to regenerate the actin monomers (G-actin), and transport of G-actin from sites of disassembly back to the leading edge completes the treadmilling cycle
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Model-Free Idealization: Adaptive Integrated Approach for Idealization of Ion Channel Currents (AI2) Biophys. J. (IF 3.4) Pub Date : 2023-08-25 Madoka Sato, Masanori Hariyama, Komiya Maki, Kae Suzuki, Yuzuru Tozawa, Hideaki Yamamoto, Ayumi Hirano-Iwata
Single-channel electrophysiological recordings provide insights into transmembrane ion permeation and channel gating mechanisms. The first step in the analysis of the recorded currents involves an "idealization" process, in which noisy raw data are classified into two discrete levels corresponding to the open and closed states of channels. This provides valuable information on the gating kinetics of
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DNA damage alters binding conformations of E. coli single-stranded DNA binding protein Biophys. J. (IF 3.4) Pub Date : 2023-08-24 Michael Morse, Francesco Navarro Roby, Mansi Kinare, James McIsaac, Mark C. Williams, Penny J. Beuning
Single-stranded DNA binding proteins (SSBs) are essential cellular components, binding to transiently exposed regions of single-stranded DNA (ssDNA) with high affinity and sequence non-specificity to coordinate DNA repair and replication. E. coli SSB (EcSSB) is a homotetramer that wraps variable lengths of ssDNA in multiple conformations (typically occupying either 65 or 35 nts), which is well-studied
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Polarimetric second harmonic generation microscopy of partially oriented fibers II. Imaging study Biophys. J. (IF 3.4) Pub Date : 2023-08-23 Mehdi Alizadeh, Fayez Habach, Mykolas Maciulis, Lukas Kontenis, Saulius Bagdonas, Serguei Krouglov, Vytautas Baranauskas, Danute Bulotiene, Vitalijus Karabanovas, Ricardas Rotomskis, Margarete K. Akens, Virginijus Barzda
Polarimetric second harmonic generation (SHG) microscopy imaging is employed to investigate the ultrastructural organization of biological and biomimetic partially oriented fibrillar structures. The linear polarization-in polarization-out (PIPO) SHG microscopy measurements are conducted with rat tail tendon, rabbit cornea, pig cartilage and biomimetic meso-tetra (4-sulfonatophenyl) porphine (TPPS4)
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Polarimetric second harmonic generation microscopy of partially oriented fibers I. Digital modeling Biophys. J. (IF 3.4) Pub Date : 2023-08-22 Mehdi Alizadeh, Serguei Krouglov, Virginijus Barzda
Second harmonic generation (SHG) in biological tissues originates predominantly from noncentrosymmetric fibrillar structures partially oriented within a focal volume (voxel) of a multiphoton excitation microscope. This study is aimed to elucidate fibrillar organization factors influencing SHG intensity, as well as achiral, R, and chiral, C, nonlinear susceptibility tensor component ratios. SHG response
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Kinetic and thermodynamic allostery in the Ras protein family Biophys. J. (IF 3.4) Pub Date : 2023-08-19 Leigh J. Manley, Milo M. Lin
Allostery, the transfer of information between distant parts of a macromolecule, is a fundamental feature of protein function and regulation. However, allosteric mechanisms are usually not explained by protein structure, requiring information on correlated fluctuations uniquely accessible to molecular simulation. Existing work to extract allosteric pathways from molecular dynamics simulations has focused
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Probing Interactions of Red Blood Cells and Contracting Fibrin Platelet Clots Biophys. J. (IF 3.4) Pub Date : 2023-08-19 Yueyi Sun, Hoyean Le, Wilbur A. Lam, Alexander Alexeev
Contraction of blood clots plays an important role in blood clotting, a natural process that restores hemostasis and regulates thrombosis in the body. Upon injury, a chain of events culminate in the formation of a soft plug of cells and fibrin fibers attaching to wound edges. Platelets become activated and apply contractile forces to shrink the overall clot size, modify clot structure, and mechanically
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Collective heterogeneity of mitochondrial potential in contact inhibition of proliferation Biophys. J. (IF 3.4) Pub Date : 2023-08-19 Basil Thurakkal, Kishore Hari, Rituraj Marwaha, Sanjay Karki, Mohit K. Jolly, Tamal Das
In the epithelium, cell density and cell proliferation are closely connected to each other through contact inhibition of proliferation (CIP). Depending on cell density, CIP proceeds through three distinct stages, namely the free-growing stage at low density, the pre-epithelial transition stage at medium density, and the post-epithelial transition stage at high density. Previous studies have elucidated
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Dynamics and spatial organization of Kv1.3 at the immunological synapse of human CD4+ T cells Biophys. J. (IF 3.4) Pub Date : 2023-08-18 Jesusa Capera, Ashwin Jainarayanan, María Navarro-Pérez, Salvatore Valvo, Philippos Demetriou, David Depoil, Irene Estadella, Audun Kvalvaag, James H. Felce, Antonio Felipe, Michael L. Dustin
Formation of the immunological synapse (IS) is a key event during initiation of an adaptive immune response to a specific antigen. During this process, a T cell and an Antigen Presenting Cell (APC) form a stable contact that allows the T cell to integrate both internal and external stimuli in order to decide whether to activate. The threshold for T cell activation depends on the strength and frequency
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Replacement of the Native cis Prolines by Alanine Simplifies the Complex Folding Mechanism of a Small Globular Protein by Eliminating both Fast and Slow phases of Folding Biophys. J. (IF 3.4) Pub Date : 2023-08-18 Anushka Kaushik, Jayant B. Udgaonkar
The folding mechanism of MNEI, a single-chain variant of naturally occurring double-chain monellin, is complex, with multiple parallel refolding channels. To determine whether its folding energy landscape could be simplified, the two native cis-prolines, Pro41 and Pro93 were mutated, singly and together, to Ala. The stability of P93A was the same as that of the wild-type protein, pWT; however, P41A
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Direct identification of the rotary angle of ATP cleavage in F1-ATPase from Bacillus PS3 Biophys. J. (IF 3.4) Pub Date : 2023-08-17 Yuh Hasimoto, Mitsuhiro Sugawa, Yoshihiro Nishiguchi, Fumihiro Aeba, Ayari Tagawa, Kenta Suga, Nobukiyo Tanaka, Hiroshi Ueno, Hiroki Yamashita, Ryuichi Yokota, Tomoko Masaike, Takayuki Nishizaka
Abstract not available
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Sarcomere mechanics in the double-actin-overlap zone Biophys. J. (IF 3.4) Pub Date : 2023-08-15 Robert Rockenfeller, Michael Günther, Scott L. Hooper
Abstract not available
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The mechanics of cephalic furrow formation in the Drosophila embryo Biophys. J. (IF 3.4) Pub Date : 2023-08-11 Redowan A. Niloy, Michael C. Holcomb, Jeffrey H. Thomas, Jerzy Blawzdziewicz
Cephalic furrow formation (CFF) is a major morphogenetic movement during gastrulation in Drosophila melanogaster embryos that gives rise to a deep, transitory epithelial invagination. Recent studies have identified the individual cell-shape changes that drive the initiation and progression phases of CFF; however, the underlying mechanics are not yet well understood. During the progression phase, the
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A Novel Design for Magnetic Tweezers with Wide-Range Temperature Control Biophys. J. (IF 3.4) Pub Date : 2023-08-10 Yu Zhou, Qingnan Tang, Xiaodan Zhao, Xiangjun Zeng, Clarence Chong, Jie Yan
Single-molecule manipulation technologies have proven to be powerful tools for studying the molecular mechanisms and physical principles underlying many essential biological processes. However, achieving wide-range temperature control has been challenging due to thermal drift that undermines the stability of the instrument. This limitation has made it difficult to study biomolecules from thermophiles
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Elasticity control of entangled chromosomes: crosstalk between condensin complexes and nucleosomes Biophys. J. (IF 3.4) Pub Date : 2023-08-10 Tetsuya Yamamoto, Kazuhisa Kinoshita, Tatsuya Hirano
Condensin-mediated loop extrusion is now considered as the main driving force of mitotic chromosome assembly. Recent experiments have shown, however, that a class of mutant condensin complexes deficient in loop extrusion can assemble chromosome-like structures in Xenopus egg extracts, although these structures are somewhat different from those assembled by wild-type condensin complexes. In the absence
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Multiscale imaging and quantitative analysis of plasma membrane protein-cortical actin interplay Biophys. J. (IF 3.4) Pub Date : 2023-08-10 Aparajita Dasgupta, Huong-Tra Ngo, Deryl Tschoerner, Nicolas Touret, Bruno da Rocha-Azevedo, Khuloud Jaqaman
The spatiotemporal organization of cell surface receptors is important for cell signaling. Cortical actin (CA), the subset of the actin cytoskeleton subjacent to the plasma membrane (PM), plays a large role in cell surface receptor organization. However, this has been shown largely through actin perturbation experiments, which raise concerns of nonspecific effects and preclude quantification of actin
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The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis Biophys. J. (IF 3.4) Pub Date : 2023-08-09 Sebastian V. Morales, Ahmad Mahmood, Jacob Pollard, Janice Mayne, Daniel Figeys, Paul W. Wiseman
Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that
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Binding of viral nuclear localization signal peptides to importin-α nuclear transport protein Biophys. J. (IF 3.4) Pub Date : 2023-08-04 Bryan M. Delfing, Xavier E. Laracuente, Audrey Olson, Kenneth W. Foreman, Mikell Paige, Kylene Kehn-Hall, Christopher Lockhart, Dmitri K. Klimov
Using all-atom replica-exchange molecular dynamics simulations, we mapped the mechanisms of binding of the nuclear localization signal (NLS) sequence from Venezuelan equine encephalitis virus (VEEV) capsid protein to importin-α (impα) transport protein. Our objective was to identify the VEEV NLS sequence fragment that confers native, experimentally resolved binding to impα as well as to study associated
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Leveraging polymer modeling to reconstruct chromatin connectivity from live images Biophys. J. (IF 3.4) Pub Date : 2023-08-04 Sayantan Dutta, Ashesh Ghosh, Alistair N. Boettiger, Andrew J. Spakowitz
Chromosomal dynamics plays a central role in a number of critical biological processes, such as transcriptional regulation, genetic recombination, and DNA replication. However, visualization of chromatin is generally limited to live imaging of a few fluorescently labeled chromosomal loci or high-resolution reconstruction of multiple loci from a single time frame. To aid in mapping the underlying chromosomal
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The interplay between adsorption and aggregation of von Willebrand factor chains in shear flows Biophys. J. (IF 3.4) Pub Date : 2023-08-03 Helman Amaya-Espinosa, Alfredo Alexander-Katz, Camilo Aponte-Santamaría
Von Willebrand factor (VWF) is a giant extracellular glycoprotein that carries out a key adhesive function during primary hemostasis. Upon vascular injury and triggered by the shear of flowing blood, VWF establishes specific interactions with several molecular partners in order to anchor platelets to collagen on the exposed sub-endothelial surface. VWF also interacts with itself to form aggregates
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Eu3+ detects two functionally distinct luminal Ca2+ binding sites in ryanodine receptors Biophys. J. (IF 3.4) Pub Date : 2023-08-02 Zsuzsanna É. Magyar, Jacob Bauer, Vladena Bauerová-Hlinková, István Jóna, Jana Gaburjakova, Marta Gaburjakova, János Almássy
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Lipid Driven Inter-leaflet Coupling of Plasma Membrane Order Regulates FcεRI Signaling in Mast Cells Biophys. J. (IF 3.4) Pub Date : 2023-08-01 Gil-Suk Yang, Alice Wagenknecht-Wiesner, Boyu Yin, Pavana Suresh, Erwin London, Barbara A. Baird, Nirmalya Bag
Inter-leaflet coupling - the influence of one leaflet on the properties of the opposing leaflet - is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn, regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by
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Nanoscale details of mitochondrial constriction revealed by cryoelectron tomography Biophys. J. (IF 3.4) Pub Date : 2023-08-01 Shrawan Kumar Mageswaran, Danielle Ann Grotjahn, Xiangrui Zeng, Benjamin Asher Barad, Michaela Medina, My Hanh Hoang, Megan J. Dobro, Yi-Wei Chang, Min Xu, Wei Yuan Yang, Grant J. Jensen
Mitochondria adapt to changing cellular environments, stress stimuli, and metabolic demands through dramatic morphological remodeling of their shape, and thus function. Such mitochondrial dynamics is often dependent on cytoskeletal filament interactions. However, the precise organization of these filamentous assemblies remains speculative. Here, we apply cryogenic electron tomography to directly image
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Push-pull mechanics of E-cadherin ectodomains in biomimetic adhesions Biophys. J. (IF 3.4) Pub Date : 2023-07-31 Kartikeya Nagendra, Adrien Izzet, Nicolas B. Judd, Ruben Zakine, Leah Friedman, Oliver J. Harrison, Léa-Laetitia Pontani, Lawrence Shapiro, Barry Honig, Jasna Brujic
E-cadherin plays a central role in cell-cell adhesion. The ectodomains of wild-type cadherins form a crystalline-like two-dimensional lattice in cell-cell interfaces mediated by both trans (apposed cell) and cis (same cell) interactions. In addition to these extracellular forces, adhesive strength is further regulated by cytosolic phenomena involving α and β catenin-mediated interactions between cadherin
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Enhancing robustness, precision, and speed of traction force microscopy with machine learning Biophys. J. (IF 3.4) Pub Date : 2023-07-31 Felix S. Kratz, Lars Möllerherm, Jan Kierfeld
Traction patterns of adherent cells provide important information on their interaction with the environment, cell migration, or tissue patterns and morphogenesis. Traction force microscopy is a method aimed at revealing these traction patterns for adherent cells on engineered substrates with known constitutive elastic properties from deformation information obtained from substrate images. Conventionally
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Real time measure of solvation free energy changes upon liquid-liquid phase separation of α-Elastin Biophys. J. (IF 3.4) Pub Date : 2023-07-28 Benedikt König, Simone Pezzotti, Sashary Ramos, Gerhard Schwaab, Martina Havenith
Biological condensates are known to retain a large fraction of water to remain in a liquid and reversible state. Local solvation contributions from water hydrating hydrophilic and hydrophobic protein surfaces were proposed to play a prominent role for the formation of condensates through liquid-liquid phase separation (LLPS). However, while the total free energy is accessible by calorimetry, the partial
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Dectin-1 multimerization and signaling depends on fungal β-glucan structure and exposure Biophys. J. (IF 3.4) Pub Date : 2023-07-27 Eduardo U. Anaya, Akram Etemadi Amin, Michael J. Wester, Michael E. Danielson, Kyle S. Michel, Aaron K. Neumann
Dectin-1A is a C-type lectin innate immunoreceptor that recognizes β-(1,3;1,6)-glucan, a structural component of Candida species cell walls. β-Glucans can adopt solution structures ranging from random coil to insoluble fiber due to tertiary (helical) and quaternary structure. Fungal β-glucans of medium and high molecular weight are highly structured, but low molecular weight glucan is much less structured
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Aha1 regulates Hsp90’s conformation and function in a stoichiometry-dependent way Biophys. J. (IF 3.4) Pub Date : 2023-07-27 Tanumoy Mondol, Laura-Marie Silbermann, Julia Schimpf, Leonie Vollmar, Bianca Hermann, Katarzyna (Kasia) Tych, Thorsten Hugel
The heat shock protein 90 (Hsp90) is a molecular chaperone, which plays a key role in eukaryotic protein homeostasis. Co-chaperones assist Hsp90 in client maturation and in regulating essential cellular processes such as cell survival, signal transduction, gene regulation, hormone signaling, and neurodegeneration. Aha1 (activator of Hsp90 ATPase) is a unique co-chaperone known to stimulate the ATP
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Real-time detection of human telomerase DNA synthesis by multiplexed single-molecule FRET Biophys. J. (IF 3.4) Pub Date : 2023-07-27 Jendrik Hentschel, Mareike Badstübner, Junhong Choi, Clive R. Bagshaw, Christopher P. Lapointe, Jinfan Wang, Linnea I. Jansson, Joseph D. Puglisi, Michael D. Stone
Genomic stability in proliferating cells critically depends on telomere maintenance by telomerase reverse transcriptase. Here we report the development and proof-of-concept results of a single-molecule approach to monitor the catalytic activity of human telomerase in real time and with single-nucleotide resolution. Using zero-mode waveguides and multicolor FRET, we recorded the processive addition
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Long ssRNA undergoes continuous compaction in the presence of polyvalent cations Biophys. J. (IF 3.4) Pub Date : 2023-07-27 Ana Luisa Duran-Meza, Liya Oster, Richard Sportsman, Martin Phillips, Charles M. Knobler, William M. Gelbart
In the presence of polyvalent cations, long double-stranded DNA (dsDNA) in dilute solution undergoes a single-molecule, first-order, phase transition (“condensation”), a phenomenon that has been documented and analyzed by many years of experimental and theoretical studies. There has been no systematic effort, however, to determine whether long single-stranded RNA (ssRNA) shows an analogous behavior
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Efficient Hi-C inversion facilitates chromatin folding mechanism discovery and structure prediction Biophys. J. (IF 3.4) Pub Date : 2023-07-26 Greg Schuette, Xinqiang Ding, Bin Zhang
Genome-wide chromosome conformation capture (Hi-C) experiments have revealed many structural features of chromatin across multiple length scales. Further understanding genome organization requires relating these discoveries to the mechanisms that establish chromatin structures and reconstructing these structures in three dimensions, but both objectives are difficult to achieve with existing algorithms
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Nonlinear effects in optical trapping of titanium dioxide and diamond nanoparticles Biophys. J. (IF 3.4) Pub Date : 2023-07-26 Anita Devi, Krishna Neupane, Haksung Jung, Keir C. Neuman, Michael T. Woodside
Optical trapping in biophysics typically uses micron-scale beads made of materials like polystyrene or glass to probe the target of interest. Using smaller beads made of higher-index materials could increase the time resolution of these measurements. We characterized the trapping of nanoscale beads made of diamond and titanium dioxide (TiO2) in a single-beam gradient trap. Calculating theoretical expectations
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Postsynaptic protein assembly in three and two dimensions studied by mesoscopic simulations Biophys. J. (IF 3.4) Pub Date : 2023-07-25 Risa Yamada, Shoji Takada
Recently, cellular biomolecular condensates formed via phase separation have received considerable attention. While they can be formed either in cytosol (denoted as 3D) or beneath the membrane (2D), the underlying difference between the two has not been well clarified. To compare the phase behaviors in 3D and 2D, postsynaptic density (PSD) serves as a model system. PSD is a protein condensate located
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A machine learning approach to predict cellular mechanical stresses in response to chemical perturbation Biophys. J. (IF 3.4) Pub Date : 2023-07-25 VigneshAravind SubramanianBalachandar, Md. Mydul Islam, R.L. Steward
Mechanical stresses generated at the cell-cell level and cell-substrate level have been suggested to be important in a host of physiological and pathological processes. However, the influence various chemical compounds have on the mechanical stresses mentioned above is poorly understood, hindering the discovery of novel therapeutics, and representing a barrier in the field. To overcome this barrier
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Fluctuations of formin binding in the generation of membrane patterns Biophys. J. (IF 3.4) Pub Date : 2023-07-24 Mary Ecke, Jana Prassler, Günther Gerisch
Circular actin waves that propagate on the substrate-attached membrane of Dictyostelium cells separate two distinct membrane domains from each other: an inner territory rich in phosphatidyl-(3,4,5) trisphosphate (PIP3) and an external area decorated with the PIP3-degrading 3-phosphatase PTEN. During wave propagation, the inner territory increases at the expense of the external area. Beyond a size limit
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ATP-induced crosslinking of a biomolecular condensate Biophys. J. (IF 3.4) Pub Date : 2023-07-21 Sebastian Coupe, Nikta Fakhri
DEAD-box helicases are important regulators of biomolecular condensates. However, the mechanisms through which these enzymes affect the dynamics of biomolecular condensates have not been systematically explored. Here, we demonstrate the mechanism by which mutation of a DEAD-box helicase’s catalytic core alters ribonucleoprotein condensate dynamics in the presence of ATP. Through altering RNA length
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Mechanics of cell-cell junctions Biophys. J. (IF 3.4) Pub Date : 2023-07-20 Yufei Wu, Sean X. Sun
Tissue cells in epithelial or endothelial monolayers are connected through cell-cell junctions, which are stabilized by transmembrane E-cadherin bonds and intracellular actin filaments. These bonds and junctions play a crucial role in maintaining the barrier function of epithelia and endothelia and are believed to transmit forces between cells. Additionally, E-cadherin bonds can impact the shape of
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Optimal cell traction forces in a generalized motor-clutch model Biophys. J. (IF 3.4) Pub Date : 2023-07-20 Roberto Alonso-Matilla, Paolo P. Provenzano, David J. Odde
Cells exert forces on mechanically compliant environments to sense stiffness, migrate, and remodel tissue. Cells can sense environmental stiffness via myosin-generated pulling forces acting on F-actin, which is in turn mechanically coupled to the environment via adhesive proteins, akin to a clutch in a drivetrain. In this “motor-clutch” framework, the force transmitted depends on the complex interplay
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Unveiling the intricacies of intracellular Ca2+ regulation in the heart Biophys. J. (IF 3.4) Pub Date : 2023-07-20 Charlotte E.R. Smith, Eleonora Grandi
Recent studies have provided valuable insight into the key mechanisms contributing to the spatiotemporal regulation of intracellular Ca2+ release and Ca2+ signaling in the heart. In this research highlight, we focus on the latest findings published in Biophysical Journal examining the structural organization of Ca2+ handling proteins and assessing the functional aspects of intracellular Ca2+ regulation
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Force generation in human blood platelets by filamentous actomyosin structures Biophys. J. (IF 3.4) Pub Date : 2023-07-20 Anna Zelená, Johannes Blumberg, Dimitri Probst, Rūta Gerasimaitė, Gražvydas Lukinavičius, Ulrich S. Schwarz, Sarah Köster
Blood platelets are central elements of the blood clotting response after wounding. Upon vessel damage, they bind to the surrounding matrix and contract the forming thrombus, thus helping to restore normal blood circulation. The hemostatic function of platelets is directly connected to their mechanics and cytoskeletal organization. The reorganization of the platelet cytoskeleton during spreading occurs
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Thermodynamics and kinetics of DNA and RNA dinucleotide hybridization to gaps and overhangs Biophys. J. (IF 3.4) Pub Date : 2023-07-19 Brennan Ashwood, Michael S. Jones, Aleksandar Radakovic, Smayan Khanna, Yumin Lee, Joseph R. Sachleben, Jack W. Szostak, Andrew L. Ferguson, Andrei Tokmakoff
Hybridization of short nucleic acid segments (<4 nt) to single-strand templates occurs as a critical intermediate in processes such as nonenzymatic nucleic acid replication and toehold-mediated strand displacement. These templates often contain adjacent duplex segments that stabilize base pairing with single-strand gaps or overhangs, but the thermodynamics and kinetics of hybridization in such contexts
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Simulations suggest robust microtubule attachment of kinesin and dynein in antagonistic pairs Biophys. J. (IF 3.4) Pub Date : 2023-07-17 Tzu-Chen Ma, Allison M. Gicking, Qingzhou Feng, William O. Hancock
Intracellular transport is propelled by kinesin and cytoplasmic dynein motors that carry membrane-bound vesicles and organelles bidirectionally along microtubule tracks. Much is known about these motors at the molecular scale, but many questions remain regarding how kinesin and dynein cooperate and compete during bidirectional cargo transport at the cellular level. The goal of the present study was
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Kinetics of radiation-induced DNA double-strand breaks through coarse-grained simulations Biophys. J. (IF 3.4) Pub Date : 2023-07-17 Manuel Micheloni, Lorenzo Petrolli, Gianluca Lattanzi, Raffaello Potestio
Double-strand breaks (DSBs), i.e., the covalent cut of the DNA backbone over both strands, are a detrimental outcome of cell irradiation, bearing chromosomal aberrations and leading to cell apoptosis. In the early stages of the evolution of a DSB, the disruption of the residual interactions between the DNA moieties drives the fracture of the helical layout; in spite of its biological significance,