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The Area Law of Molecular Entropy: Moving Beyond Harmonic Approximation. bioRxiv. Biophys. Pub Date : 2024-03-17 Amitava Roy, Vishwesh Venkatraman, Tibra Ali
Inspired by black hole thermodynamics, the area law that entropy is proportional to horizon area has been proposed in quantum entanglement entropy and has largely maintained its validity. This article shows that the area law is also valid for the thermodynamic entropy of molecules. We showed that the gas-phase entropy of molecules obeys the area law with our proposed correction for the different curvatures
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LIPIDS MODULATE THE DYNAMICS OF GPCR:β-ARRESTIN INTERACTION bioRxiv. Biophys. Pub Date : 2024-03-17 Angoniel Augusto Severo GOMES, Michela DI MICHELE, Rita Ann ROESSNER, Marjorie DAMIAN, Paulo Mascarello BISCH, Nathalie SIBILLE, Maxime LOUET, Jean-Louis BANERES, Nicolas FLOQUET
β-arrestins are key privileged molecular partners of G-Protein Coupled Receptors (GPCRs), triggering not only their desensitization but also intracellular signaling. Existing structures point to a high conformational plasticity of β-arrestin:GPCRs interaction, with two completely different orientations between receptor and β-arrestin. The same set of structures also indicates that the C-edge loop of
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The growth-driven penetration strategy of plant roots is mechanically more efficient than pushing bioRxiv. Biophys. Pub Date : 2024-03-17 Yoni Koren, Alessia Perilli, Oren Tchaicheeyan, Ayelet Lesman, Yasmine Meroz
Plant roots are considered highly efficient soil explorers. As opposed to the push-driven penetration strategy commonly used by many digging organisms, roots penetrate by growing, adding new cells at the tip, and elongating over a well-defined growth zone. However, a comprehensive understanding of the mechanical aspects associated with root penetration is currently lacking. We perform penetration experiments
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Conditions for the co-existence of promoter and gene-body condensates bioRxiv. Biophys. Pub Date : 2024-03-17 Arya Changiarath, Jasper Michels, Rosa Herrera Rodriguez, Sonya M Hanson, Friederike Schmid, Jan Padeken, Lukas S Stelzl
In cells, transcription is tightly regulated on multiple layers. The condensation of the transcription machinery into distinct phases is hypothesized to spatio-temporally fine tune RNA polymerase II behaviour during two key stages, transcription initiation and the elongation of the nascent RNA transcripts. However, it has remained unclear whether these phases would mix when present at the same time
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HIV integrase compacts viral DNA into biphasic condensates bioRxiv. Biophys. Pub Date : 2024-03-17 Pauline Julika Kolbeck, Marjolein de Jager, Margherita Gallano, Tine Brouns, Ben Bekaert, Wout Frederickx, Sebastian Ferdinand Konrad, Siska Van Belle, Frauke Christ, Steven De Feyter, Zeger Debyser, Laura Christine Filion, Jan Lipfert, Willem Vanderlinden
The human immunodeficiency virus (HIV) infects non-dividing cells and its genome must be compacted to enter the cell nucleus. Here, we show that the viral enzyme integrase (IN) compacts HIV DNA mimetics in vitro. Under physiological conditions, IN-compacted genomes are consistent in size with those found for pre-integration complexes in infected cells. Compaction occurs in two stages: first IN tetramers
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A λ-dynamics investigation of insulin Wakayama and other A3 variant binding affinities to the insulin receptor bioRxiv. Biophys. Pub Date : 2024-03-17 Monica P Barron, Jonah Z Vilseck
Insulin Wakayama is a clinical insulin variant where a conserved valine at the third residue on insulin's A chain (ValA3) is replaced with a leucine (LeuA3), impairing insulin receptor (IR) binding by 140-500 fold. This severe impact on binding from such a subtle modification has posed an intriguing problem for decades. Although experimental investigations of natural and unnatural A3 mutations have
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Live imaging of Alu elements reveals non-uniform euchromatin dynamics coupled to transcription bioRxiv. Biophys. Pub Date : 2024-03-17 Yi-Che Chang, Sofia A Quinodoz, Clifford P Brangwynne
Chromatin structure and dynamics are crucial for eukaryotic nuclear functions. Hi-C and related genomic assays have revealed chromatin conformations, such as A/B compartments, in fixed cells, but the dynamic motion of such structures is not well understood. Moreover, elucidating the relationship between the motion of chromatin and transcriptional activity is hampered by a lack of tools for specifically
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Heterotypic Seeding Generates Mixed Amyloid Polymorphs bioRxiv. Biophys. Pub Date : 2024-03-17 Siddhartha Banerjee, Divya Baghel, Harrison O Edmonds, Ayanjeet Ghosh
Aggregation of the amyloid beta (Abeta) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimers disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Abeta; on the structure
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Dependence of Nucleosome Mechanical Stability on DNA Mismatches bioRxiv. Biophys. Pub Date : 2024-03-17 Thuy T. M. Ngo, Bailey Liu, Feng Wang, Aakash Basu, Carl Wu, Taekjip Ha
The organization of nucleosomes into chromatin and their accessibility are shaped by local DNA mechanics. Conversely, nucleosome positions shape genetic variations, which may originate from mismatches during replication and chemical modification of DNA. To investigate how DNA mismatches affect the mechanical stability and the exposure of nucleosomal DNA, we used an optical trap combined with single-molecule
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Prediction of Ca2+ binding site in proteins with a fast and accurate method based on statistical mechanics and analysis of crystal structures bioRxiv. Biophys. Pub Date : 2024-03-17 Abdul Basit, Devapriya Choudhury, Pradipta Bandyopadhyay
Predicting the precise locations of metal binding sites within metalloproteins is a crucial challenge in biophysics. It is challenging for both experimental and computational approaches. In the current work, we have predicted the location of Ca2+ ions in calcium-binding proteins using a physics-based method with an all-atom description of the proteins, which is substantially faster than the molecular
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Assessing the hydromechanical control of plant growth bioRxiv. Biophys. Pub Date : 2024-03-16 Valentin Laplaud, Elise Muller, Natalia Demidova, Stéphanie Drevensek, Arezki Boudaoud
Multicellular organisms grow and acquire their shapes through the differential expansion and deformation of their cells. Recent research has addressed the role of cell and tissue mechanical properties in these processes. In plants, it is believed that growth rate is a function of the mechanical stress exerted on the cell wall, the thin polymeric layer surrounding cells, involving an effective viscosity
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Helical Twists and beta-Turns in Structures at Serine-Proline Sequences: Stabilization of cis-Proline and type VI beta-turns via C-H/O interactions bioRxiv. Biophys. Pub Date : 2024-03-16 Harrison C Oven, Glenn P. A. Yap, Neal J Zondlo
Structures at serine-proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)-(4-iodophenyl)hydroxyproline [hyp(4-I-Ph)]. The crystal structure of Boc-Ser-hyp(4-I-Ph)-OMe had two molecules in the unit cell. One molecule exhibited cis-proline and a type
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Understanding the binding mechanisms of Alzheimer risk factor TREM2 in lipid bilayer using multi-scale molecular dynamics simulations bioRxiv. Biophys. Pub Date : 2024-03-16 Zhiwen Zhong, Martin Ulmschneider, Chris Lorenz
Alzheimer's disease (AD) is a widespread neurodegenerative condition affecting millions globally. Recent research has implicated variants of the triggering receptor expressed in myeloid cells 2 (TREM2) as risk factors for AD. TREM2, an immunomodulatory receptor on microglial surfaces, plays a pivotal role in regulating microglial activation by associating with DNAX-activation protein 12 (DAP12). Despite
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Hour-long, kilohertz sampling rate 3D single-virus tracking in live cells enabled by StayGold fluorescent protein fusions bioRxiv. Biophys. Pub Date : 2024-03-15 Yuxin Lin, Jack Exell, Haoting Lin, Chen Zhang, Kevin D. Welsher
The viral infection process covers a large range of spatiotemporal scales. Tracking the viral infection process with fluorescent labels over long durations while maintaining a fast sampling rate requires bright and highly photostable labels. StayGold is a recently identified green fluorescent protein that has a greater photostability and higher signal intensity under identical illumination conditions
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Predicting absolute protein folding stability using generative models bioRxiv. Biophys. Pub Date : 2024-03-15 Matteo Cagiada, Sergey Ovchinnikov, Kresten Lindorff-Larsen
While there has been substantial progress in our ability to predict changes in protein stability due to amino acid substitutions, progress has been slow in methods to predict the absolute stability of a protein. Here we show how a generative model for protein sequence can be leveraged to predict absolute protein stability. We benchmark our predictions across a broad set of proteins and find a mean
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Lipophilic compounds restore wt function of neurodevelopmental-associated KCNQ3 mutations. bioRxiv. Biophys. Pub Date : 2024-03-15 Michaela A Edmond, Andy Hinojo-Perez, Mekedlawit Efrem, Yi-Chun Lin, Iqra Shams, Sebastien Hayoz, Alicia de la Cruz, Marta E Perez rodriguez, Maykelis Diaz-Solares, Derek M Dykxhoorn, Yun Luo, Rene Barro Soria
A major driver of neuronal hyperexcitability is dysfunction of K+ channels, including voltage-gated KCNQ2/3 channels. Their slow activation and deactivation kinetics produces a current that regulates membrane potential and impedes repetitive firing. Mutations in KCNQ2 and KCNQ3 lead to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic
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How motility drives the glassy dynamics in confluent epithelial monolayers? bioRxiv. Biophys. Pub Date : 2024-03-15 Souvik Sadhukhan, Manoj Kumar Nandi, Satyam Pandey, Matteo Paoluzzi, Chandan Dasgupta, Nir Gov, Saroj Kumar Nandi
As wounds heal, embryos develop, cancer spreads, or asthma progresses, the cellular monolayer undergoes a glass transition from a solid-like jammed to a fluid-like flowing state. Two primary characteristics of these systems, confluency, and self-propulsion, make them distinct from particulate systems. Are the glassy dynamics in these biological systems and equilibrium particulate systems different
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Molecular Insights into the Rescue Mechanism of an hERG Activator Against Severe LQT2 Mutations. bioRxiv. Biophys. Pub Date : 2024-03-15 Amit Kumawat, Elisa Tavazzani, Giovanni Lentini, Alessandro Trancuccio, Deni Kukavica, Marco Denegri, Silvia G Priori, Carlo Camilloni
Mutations in the hERG potassium channel are a major cause of long QT syndrome type 2 (LQT2), which can lead to sudden cardiac death. The hERG channel plays a critical role in the repolarization of the myocardial action potential, and loss-of-function mutations prolong cardiac repolarization. In this study, we investigated the efficacy and mechanism of ICA-105574, an hERG activator, in shortening the
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Proofreading and single-molecule sensitivity in T-cell receptor signaling by condensate nucleation bioRxiv. Biophys. Pub Date : 2024-03-15 William L White, David Baker, Jay T Groves, David Baker, Ariel Jaques Ben-sasson, Hao Yuan Kueh
T-cells display the remarkable ability to detect single foreign peptides displayed on target cells, while ignoring highly abundant self peptides. This selectivity has been explained by kinetic proofreading in the T-cell receptor (TCR) signaling pathway, which prevents responses to short-lived binding events regardless of their abundance. However, the biochemical mechanisms that drive kinetic proofreading
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A physically inspired approach to coarse-graining transcriptomes reveals the dynamics of aging: multiscale description of gene expressions and a spectral view of aging dynamics bioRxiv. Biophys. Pub Date : 2024-03-15 Tao Li, Madhav Mani
Single-cell RNA sequencing has enabled the study of aging at a molecular scale. While substantial progress has been made in measuring age-related gene expression, the underlying patterns and mechanisms of aging transcriptomes remain poorly understood. To address this gap, we propose a physics-inspired, data-analysis approach to extract additional insights from single-cell RNA sequencing data. By considering
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Intracellular mechanical fingerprint reveals cell type specific mechanical tuning bioRxiv. Biophys. Pub Date : 2024-03-15 Till M. Muenker, Bart E Vos, Timo Betz
Living cells are complex entities that perform many different complex tasks with astonishing robustness. While the direct dependence of biological processes on controlled protein expression is well established, we only begin to understand how intracellular mechanical characteristics guide and support biological function. This is in stark contrast to the expected functional role that intracellular mechanical
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Physical basis for the interaction between Drosophila ROS1 and the GPCR BOSS bioRxiv. Biophys. Pub Date : 2024-03-14 Jianan Zhang, Yuko Tsutsui, Hengyi Li, Tongqing Li, Yueyue Wang, Daryl Ewald Klein
Drosophila ROS1 (dROS1, Sevenless) is a receptor tyrosine kinase (RTK) essential for the differentiation of Drosophila R7 photoreceptor cells. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells. Genetic evidence together with in vitro activity assays confirmed the activation of dROS1 by BOSS
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Biophysical metabolic modeling of complex bacterial colony morphology bioRxiv. Biophys. Pub Date : 2024-03-14 Ilija Dukovski, Lauren Golden, Jing Zhang, Melisa Osborne, Daniel Segrè, Kirill Korolev
Microbial colony growth is shaped by the physics of biomass propagation and nutrient diffusion, and by the metabolic reactions that organisms activate as a function of the surrounding environment. While microbial colonies have been explored using minimal models of growth and motility, full integration of biomass propagation and metabolism is still lacking. Here, building upon our framework for Computation
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A possible path to persistent re-entry waves at the outlet of the left pulmonary vein bioRxiv. Biophys. Pub Date : 2024-03-14 Karoline Horgmo Jaeger, Aslak Tveito
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, often evolving from paroxysmal episodes to persistent stages over an extended timeframe. While various factors contribute to this progression, the precise biophysical mechanisms driving it remain unclear. Here we explore how rapid firing of cardiomyocytes at the outlet of the pulmonary vein of the left atria can create a substrate
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Allometric multi-scaling of weight-for-height relation in children and adolescents: Revisiting the theoretical basis of body mass index of thinness and obesity assessment bioRxiv. Biophys. Pub Date : 2024-03-14 Hitomi Ogata, Sayaka Nose-Ogura, Narumi Nagai, Momoko Kayaba, Yosuke Isoyam, Joao Gabriel Segato Kruse, Ivan Selezno, Miki Kaneko, Taiki Shigematsu, Ken Kiyono
The body mass index (BMI), defined as weight in kilograms divided by height in meters squared, has been widely used to assess thinness and obesity in all age groups, including children and adolescents. However, the validity and utility of BMI as a reliable measure of nutritional health have been questioned. This study discusses the mathematical conditions that support the validity of BMI based on population
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Quantifying Induced Dipole Effects in Small Molecule Permeation in a Model Phospholipid Bilayer bioRxiv. Biophys. Pub Date : 2024-03-14 Julia M Montgomery, Justin A Lemkul
The cell membrane functions as a semi-permeable barrier that governs the transport of materials into and out of cells. The bilayer features a distinct dielectric gradient due to the amphiphilic nature of its lipid components. This gradient influences various aspects of small molecule permeation and the folding and functioning of membrane proteins. Here, we employ polarizable molecular dynamics simulations
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Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy bioRxiv. Biophys. Pub Date : 2024-03-14 Ruth M. Saecker, Andreas U. Mueller, Brandon Malone, James Chen, William Chase Budell, Venkata P. Dandey, Kashyap Maruthi, Joshua H. Mendez, Nina Molina, Edward T Eng, Laura Y. Yen, Clinton S. Potter, Bridget Carragher, Seth A Darst
During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAP), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, time-resolved cryo-electron microscopy (cryo-EM) was used to capture four intermediates populated 120 or 500 milliseconds (ms)
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Diffusive lensing as a mechanism of intracellular transport and compartmentalization bioRxiv. Biophys. Pub Date : 2024-03-13 Achuthan Raja Venkatesh, Kathy H Le, David M Weld, Onn Brandman
While inhomogeneous diffusivity has been identified as a ubiquitous feature of the cellular interior, its implications for particle mobility and concentration at different length scales remain largely unexplored. In this work, we use agent-based simulations of diffusion to investigate how heterogeneous diffusivity affects movement and concentration of diffusing particles. We propose that a nonequilibrium
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Membrane Lipid Domains Modulate HCN Channels in Nociceptor DRG Neurons bioRxiv. Biophys. Pub Date : 2024-03-13 Lucas J Handlin, Natalie L Macchi, Nicolas Dumaire, Lyuba Salih, Kyle S McCommis, Aubin Moutal, Gucan Dai
Cell membranes consist of heterogeneous lipid domains that influence key cellular processes, including signal transduction, endocytosis, and electrical excitability. Using FRET-based fluorescent assays and fluorescence lifetime imaging microscopy (FLIM), we found that the dimension of cholesterol-enriched ordered membrane domains (OMD) varies considerably, depending on specific cell types. The size
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PIP2-Dependent Thermoring Basis for Cold-Sensing of the TRPM8 Biothermometer bioRxiv. Biophys. Pub Date : 2024-03-13 Guangyu Wang
The menthol sensor TRPM8 can be activated by cold and thus serves as a biothermometer in a primary afferent sensory neuron for innocuous-to-noxious cold detection. However, the precise structural origins of specific temperature thresholds and sensitivity have remained elusive. Here, a grid thermodynamic model was employed to examine if the temperature-dependent noncovalent interactions found in the
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Two-photon excitation two-dimensional fluorescence spectroscopy (2PE-2DFS) of the fluorescent nucleobase 6-MI bioRxiv. Biophys. Pub Date : 2024-03-13 Claire S. Albrecht, Lawrence F. Scatena, Peter H. von Hippel, Andrew H. Marcus
Base stacking is fundamentally important to the stability of double-stranded DNA. However, few experiments can directly probe the local conformations and conformational fluctuations of the DNA bases. Here we report a new spectroscopic approach to study the local conformations of DNA bases using the UV-absorbing fluorescent guanine analogue, 6-methyl isoxanthopterin (6-MI), which can be used as a site-specific
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A metastasis-associated Pannexin1 mutant (Panx11-89) forms a minimalist ATP release channel bioRxiv. Biophys. Pub Date : 2024-03-13 Junjie Wang, Carsten Mim, Gerhard Dahl, Rene Barro-Soria
A truncated form of the ATP release channel pannexin 1 (Panx1), Panx11-89, is enriched in metastatic breast cancer cells and has been proposed to mediate metastatic cell survival by increasing ATP release through mechanosensitive Panx1 channels. However, whether Panx11-89 on its own (without the presence of wtPanx1) mediates ATP release has not been tested. Here, we show that Panx11-89 by itself can
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Self-organisation of mortal filaments: the role of FtsZ treadmilling in bacterial division ring formation bioRxiv. Biophys. Pub Date : 2024-03-13 Christian Vanhille Campos, Kevin D Whitley, Philipp Radler, Martin Loose, Seamus Holden, Andela Saric
Protein filaments in the cell commonly treadmill - they grow on one end while shrinking on the other, driven by energy consumption. Treadmilling filaments appear to be moving, even though individual proteins remain static. Here, we investigate the role of treadmilling, implemented as dynamic turnover, in the collective filament self-organisation. On the example of the bacterial FtsZ protein, a highly
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Controlled Protein-Membrane Interactions Regulate Self-Organization of Min Protein Patterns bioRxiv. Biophys. Pub Date : 2024-03-13 Mergime Hasani, Katharina Esch, Katja Zieske
Self-organizing protein patterns play an essential role in life, governing important cellular processes, such as polarization and division. While the field of protein self-organization has reached a point where basic pattern-forming mechanisms can be reconstituted in vitro using purified proteins, understanding how cells can dynamically switch and modulate these patterns, especially when transiently
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Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization bioRxiv. Biophys. Pub Date : 2024-03-13 Hossein Salari, Genevieve Fourel, Daniel Jost
Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate the relationship between gene transcription and 3D gene folding. Our analysis uncovers
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Robust cytoplasmic partitioning by solving an intrinsic cytoskeletal instability bioRxiv. Biophys. Pub Date : 2024-03-13 Melissa Rinaldin, Alison Kickuth, Benjamin Dalton, Yitong Xu, Stefano Di Talia, Jan Brugues
Early development across vertebrates and insects critically relies on robustly reorganizing the cytoplasm of fertilized eggs into individualized cells. This intricate process is orchestrated by large microtubule structures that traverse the embryo, partitioning the cytoplasm into physically distinct and stable compartments. Despite the robustness of embryonic development, here we uncover an intrinsic
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Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics bioRxiv. Biophys. Pub Date : 2024-03-12 Claire A. Dessalles, Nicolas Cuny, Arthur Boutillon, Paul F. Salipante, Avin Babataheri, Abdul I. Barakat, Guillaume Salbreux
Blood vessels expand and contract actively, while continuously experiencing dynamic external stresses from the blood flow. The mechanical response of the vessel wall is that of a composite material: its mechanical properties depend on a diverse set of cellular mechanical components, which change dynamically as cells respond to external stress. Mapping the relationship between these underlying cellular
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A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs bioRxiv. Biophys. Pub Date : 2024-03-12 Caroline Brown, Snehasish Ghosh, Rachel McAllister, Mukesh Kumar, Gerard Walker, Eric Sun, Talat Aman, Aniruddha Panda, Shailesh Kumar, Wenxue V Li, Jeff Coleman, Yansheng Liu, James E Rothman, Moitrayee Bhattacharyya, Kallol Gupta
The intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the
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Three-dimensional spatio-angular fluorescence microscopy with a polarized dual-view inverted selective-plane illumination microscope (pol-diSPIM) bioRxiv. Biophys. Pub Date : 2024-03-12 Talon Chandler, Min Guo, Yijun Su, Jiji Chen, Yicong Wu, Junyu Liu, Atharva Agashe, Robert S. Fischer, Shalin B. Mehta, Abhishek Kumar, Tobias I. Baskin, Valentin Jamouille, Huafeng Liu, Vinay Swaminathan, Amrinder Nain, Rudolf Oldenbourg, Patrick La Riviere, Hari Shroff
Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the three-dimensional orientations and diffraction-limited positions of ensembles of fluorescent dipoles that label biological structures
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Structural insights into physiological activation and antagonism of melanin-concentrating hormone receptor MCHR1 bioRxiv. Biophys. Pub Date : 2024-03-12 Xiaofan Ye, Guibing Liu, Xiu Li, Binbin He, Yuyong Tao, Weimin Gong, Haiping Liu
Melanin-concentrating hormone (MCH) is a 19-amino-acid neuropeptide playing crucial roles in energy homeostasis, sleep, and various physiological processes. It acts through two G protein-coupled receptors, MCHR1 and MCHR2, with MCHR1 being universally present in mammals and a potential target for treating metabolic and mental health conditions. However, drug development efforts have been impeded by
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VISUALIZING THE NUCLEATING AND CAPPED STATES OF F-ACTIN BY Ca2+-GELSOLIN: SAXS DATA BASED STRUCTURES OF BINARY AND TERNARY COMPLEXES bioRxiv. Biophys. Pub Date : 2024-03-12 Amin Sagar, Nagesh Peddada, Vikas CHOUDHARY, Yawar Mir, Renu Garg, Fnu Ashish
Structural insight eludes on how full-length gelsolin depolymerizes and caps F-actin, while the same entity can nucleate polymerization of G-actins. Employing small angle X-ray scattering (SAXS) data analysis, we deciphered these two contrasting assemblies. Mixing Ca2+-gelsolin with F-actin in high salt F-buffer resulted in depolymerization of ordered F-actin rods to smaller sized species which became
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Scaling of stochastic growth and division dynamics: A comparative study of individual rod-shaped cells in the Mother Machine and SChemostat platforms bioRxiv. Biophys. Pub Date : 2024-03-12 Karl F. Ziegler, Kunaal Joshi, Charles S. Wright, Shaswata Roy, Will Caruso, Rudro R. Biswas, Srividya Iyer-Biswas
Microfluidic platforms enable long-term quantification of stochastic behaviors of individual bacterial cells under precisely controlled growth conditions. Yet, quantitative comparisons of physiological parameters and cell behaviors of different microorganisms in different experimental and device modalities is not readily possible owing to experiment-specific details affecting cell physiology in confounding
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Comparative Pore Structure and Dynamics for Bacterial Microcompartment Shell Protein Assemblies in Sheets or Shells bioRxiv. Biophys. Pub Date : 2024-03-12 Saad Raza, Daipayan Sarkar, Leanne Jade G Chan, Joshua Mae, Markus Sutter, Christopher J Petzold, Cheryl A Kerfeld, Corie Y Ralston, Sayan Gupta, Josh V Vermaas
Bacterial microcompartments (BMCs) are protein-bound organelles found in some bacteria which encapsulate enzymes for enhanced catalytic activity. These compartments spatially sequester enzymes within semi-permeable shell proteins, analogous to many membrane-bound organelles. The shell proteins assemble into multimeric tiles, typically trimers, hexamers, or pentamers, and these tiles assemble into larger
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Fatiguing Exercise Reduces Cellular Passive Young's Modulus in Human Vastus Lateralis Muscle bioRxiv. Biophys. Pub Date : 2024-03-12 Grace E Privett, Austin W Ricci, Larry David, Karen W Needham, Yong How Tan, Karina H Nakayama, Damien M Callahan
Previous studies demonstrated that acute, exercise-induced fatigue transiently reduces whole-muscle stiffness. Because reduced muscle stiffness at fatigue may contribute to increased injury risk and impaired contractile performance, the present study seeks to elucidate potential intracellular mechanisms underlying these reductions. To that end, cellular passive Young's Modulus was measured in single
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Post-Translational Modifications Control Phase Transitions of Tau bioRxiv. Biophys. Pub Date : 2024-03-12 Wyatt Powell, McKinley Nahum, Karl Pankratz, Morgane Herlory, James Greenwood, Darya Poliyenko, Patrick Holland, Ruiheng Jing, Luke Biggerstaff, Michael Stowell, Maciej Walczak
The self-assembly of Tau(297-391) into filaments, which mirror the structures observed in Alzheimer's disease (AD) brains, raises questions about the role of AD-specific post-translational modifications (PTMs) in the formation of paired helical filaments (PHFs). To investigate this, we developed a synthetic approach to produce Tau(291-391) featuring N-acetyllysine, phosphoserine, phosphotyrosine, and
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Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility bioRxiv. Biophys. Pub Date : 2024-03-12 Ankit Garg, Silvia Jansen, Rui Zhang, Kory Lavine, Michael J Greenberg
Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1's high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how
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A Way to Understand Dynamics of Infantile Myoclonic Encephalopathy bioRxiv. Biophys. Pub Date : 2024-03-12 Vishal Verma
The goal of this paper is to introduce scientists (especially, paediatrics) to the mathematics that may help understand the dynamics of metabolic epilepsies like glycine encephalopathies quantitatively. The methods include the Wilson Cowan Model coupled with an adaptive control system and the neural energy consumption calculations available in the literature. The present study applies the Liu & Ching
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Molecular mechanism of parental H3/H4 recycling at a replication fork bioRxiv. Biophys. Pub Date : 2024-03-12 Fritz Nagae, Yasuto Murayama, Tsuyoshi Terakawa
In eukaryotic chromatin replication, faithful recycling of histones from parental DNA to replicated leading and lagging strands is essential for maintaining epigenetic information across generations. A recent experimental study has revealed that disrupting interactions between the N-terminal disordered tail of Mcm2, a subunit in DNA replication machinery, and a histone H3/H4 tetramer, a carrier of
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DNA-based ForceChrono Probes for Deciphering Single-Molecule Force Dynamics in Living Cells bioRxiv. Biophys. Pub Date : 2024-03-12 Yuru Hu, Hongyun Li, Chen Zhang, Jingjing Feng, Wenxu Wang, Wei Chen, Miao Yu, Xinghua Zhang, Zheng Liu
Accurate measurement of mechanical forces in cells is key to understanding how cells sense and respond to mechanical stimuli, a central aspect of mechanobiology. However, accurately quantifying dynamic forces at the single-molecule level in living cells is a significant challenge. Here, we've developed the DNA-based ForceChrono probe to enable in-depth studies of integrin force dynamics at the single-molecule
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Tipping-point transition from transient to persistent inflammation in pancreatic islets bioRxiv. Biophys. Pub Date : 2024-03-12 Thomas Holst Hansen, Pernille Yde Nielsen, Mogens Hoegh Jensen, Thomas Mandrup-Poulsen, Ala Trusina
Type 2 diabetes (T2D) is associated with a systemic increase in the pro-inflammatory cytokine IL-1beta. While transient exposure to low IL-1beta concentrations improves insulin secretion and beta-cell proliferation in pancreatic islets, prolonged exposure leads to impaired insulin secretion and collective beta-cell death. IL-1 is secreted locally by islet-resident macrophages and beta-cells; however
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Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases bioRxiv. Biophys. Pub Date : 2024-03-12 Joan Gizzio, Abhishek Thakur, Allan Haldane, Ronald Levy
Protein kinases are molecular machines with rich sequence variation that distinguishes the two main evolutionary branches: tyrosine kinases (TKs) from serine/threonine kinases (STKs). Using a sequence co-variation Potts statistical energy model we previously concluded that TK catalytic domains are more likely than STKs to adopt an inactive conformation with the activation loop in an autoinhibitory
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Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging bioRxiv. Biophys. Pub Date : 2024-03-12 Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Ben Fellows, A. Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan
Introduction: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. Methods: Human-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours
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A subtle modification of modafinil-based DAT inhibitors changes conformational preference bioRxiv. Biophys. Pub Date : 2024-03-12 Kuo Hao Lee, Gisela Andrea Camacho-Hernandez, Amy Hauck Newman, Lei Shi
Modafinil analogs with either a sulfoxide or sulfide moiety have improved binding affinities at the human dopamine transporter (hDAT) compared to modafinil, with lead sulfoxide-substituted analogs showing characteristics of atypical inhibition (e.g., JJC8-091). Interestingly, the only distinction between sulfoxide and sulfide substitution is the presence of one additional oxygen atom. To elucidate
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Controlling Drug Partitioning in Individual Protein Condensates through Laser-Induced Microscale Phase Transitions. bioRxiv. Biophys. Pub Date : 2024-03-12 Axel Leppert, Feng Jianhui, Vaida Railaite, Tomas Bohn Pessatti, Cecilia Morman, Hannah Osterholz, Filipe R N C Maia, Markus B. Linder, Anna Rising, Michael Landreh
Gelation of protein condensates formed by liquid-liquid phase separation (LLPS) occurs in a wide range of biological con-texts, from the assembly of biomaterials to the formation of fibrillar aggregates and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting
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DNA replication and polymer chain duplication reshape the genome in space and time bioRxiv. Biophys. Pub Date : 2024-03-12 Dario D'Asaro, Maxime MC Tortora, Cedric Vaillant, Jean-Michel Arbona, Daniel Jost
In eukaryotes, DNA replication constitutes a complex process whereby multiple origins are stochastically fired, and from which the replication machinery proceeds along chromosomes to achieve the faithful synthesis of two identical copies of the genome during the S-phase of the cell cycle. Experimental evidence show a functional correlation between the dynamics of replication and the spatial organization
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Mechanistic insights into transport models of the sphingolipid transport protein, Spinster homolog 2 (Spns2), using MD simulations bioRxiv. Biophys. Pub Date : 2024-03-12 Amanda K. Sharp, Marion Q. LoPresti, Anne M. Brown
Sphingosine-1-phosphate (S1P) is a sphingolipid signaling molecule that when elevated results in multiple disease states including metastatic cancers. Modulating the extracellular concentrations of S1P has been an evolving strategy in drug development for metastatic cancers due to its role in angiogenesis and cell migration. Research has shown that Spns2, the S1P transport protein, is an important
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IP6 and PF74 affect HIV-1 Capsid Stability through Modulation of Hexamer-Hexamer Tilt Angle Preference bioRxiv. Biophys. Pub Date : 2024-03-12 Chris M Garza, Matthew Holcomb, Diogo Santos-Martins, Bruce E. Torbett, Stefano Forli
The HIV-1 capsid is an irregularly shaped complex of about 1200 protein chains containing the viral genome and several viral proteins. Together, these components are the key to unlocking passage into the nucleus, allowing for permanent integration of the viral genome into the host cell genome. Recent interest into the role of the capsid in viral replication has been driven by the approval of the first-in-class
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Competitive assembly resolves the stoichiometry of essential proteins in infectious HIV-1 virions. bioRxiv. Biophys. Pub Date : 2024-03-12 Haley Durden, Benjamin Preece, Rodrigo Gallegos, Ipsita Saha, Brian MacArthur, Abby Petersen, Wiley Peppel, Saveez Saffarian
During assembly on the plasma membrane, HIV-1 virions incorporate Gag-Pol as well as gp120/gp41 trimers. The Pol region consists of protease, reverse transcriptase and integrase precursors which are essential enzymes required for maturation, reverse transcription, and integration of the viral genome in the next host. gp120/gp41 trimers catalyze the fusion of the virion with its next host. Only a fraction
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Stochastic Voronoi Tessellations as Models for Cellular Neighborhoods in Simple Multicellular Organisms bioRxiv. Biophys. Pub Date : 2024-03-12 Anand Srinivasan, Steph S.M.H. Hohn, Raymond E. Goldstein
Recent work on distinct multicellular organisms has revealed a hitherto unknown type of biological noise; rather than a regular arrangement, cellular neighborhood volumes, obtained by Voronoi tessellations of the cell locations, are broadly distributed and consistent with gamma distributions. We propose an explanation for those observations in the case of the alga Volvox, whose somatic cells are embedded
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Cell-cycle and Age-Related Modulations in Mouse Chromosome Stiffness bioRxiv. Biophys. Pub Date : 2024-03-11 Ning Liu, Wenan Qiang, Philip Jordan, John F Marko, Huanyu Qiao
The intricate structure of chromosomes is complex, and many aspects of chromosome configuration/organization remain to be fully understood. Measuring chromosome stiffness can provide valuable insights into their structure. However, the nature of chromosome stiffness, whether static or dynamic, remains elusive. In this study, we analyzed chromosome stiffness in MI and MII oocytes. We revealed that MI