Top 9 Biorxiv Papers Today in Biophysics


2.041 Mikeys
#1. Cell-derived plasma membrane vesicles are permeable to hydrophilic macromolecules
Allison D Skinkle, Ilya Levental
Giant Plasma Membrane Vesicles (GPMVs) are a widely used model system for biochemical and biophysical analysis of the isolated mammalian plasma membrane (PM). A core advantage of these vesicles is that they maintain the native lipid and protein diversity of the plasma membrane while affording the experimental flexibility of synthetic giant vesicles. In addition to fundamental investigations of PM structure and composition, GPMVs have been used to evaluate the binding of proteins and small molecules to cell-derived membranes, and the permeation of drug-like molecules through them. An important assumption of such experiments is that GPMVs are sealed; i.e. that permeation occurs by diffusion through the hydrophobic core rather than through hydrophilic pores. Here we demonstrate that this assumption is often incorrect. We find that most GPMVs isolated using standard preparations are passively permeable to various hydrophilic solutes as large as 40 kDa, in contrast to synthetic giant unilamellar vesicles (GUVs). We attribute this...
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biorxivpreprint: Cell-derived plasma membrane vesicles are permeable to hydrophilic macromolecules https://t.co/uPvMLCzqjn #bioRxiv
biorxiv_biophys: Cell-derived plasma membrane vesicles are permeable to hydrophilic macromolecules https://t.co/KpmbChAh3s #biorxiv_biophys
nadlerlab: Everybody working with GPMVs needs to read this ASAP: https://t.co/jHhNUEaFn9 Standard GPMVs are super-leaky - and there's a cool solution to the problem.
kwitschas: RT @biorxiv_biophys: Cell-derived plasma membrane vesicles are permeable to hydrophilic macromolecules https://t.co/KpmbChAh3s #biorxiv_bi…
kschink: RT @nadlerlab: Everybody working with GPMVs needs to read this ASAP: https://t.co/jHhNUEaFn9 Standard GPMVs are super-leaky - and there's a…
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Authors: 2
Total Words: 0
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2.01 Mikeys
#2. Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations
Marharyta G. Petukh, Davi R. Ortega, Jerome Baudry, Igor B. Zhulin
Chemoreceptors are principal components of the bacterial sensory system that modulates cellular motility. They detect changes in the environment and transmit information to CheA histidine kinase, which ultimately controls cellular flagellar motors. The prototypical Tsr chemoreceptor in E. coli is a homodimer containing two principal functional modules: (i) a periplasmic ligand-binding domain and (ii) a cytoplasmic signaling domain. Chemoreceptor dimers are arranged into a trimer of dimers at the tip of the signaling domain comprising a minimal physical unit essential for enhancing the CheA activity several hundredfold. Trimers of dimers are arranged into highly ordered hexagon arrays at the cell pole; however, the mechanism underlying the trimer-of-dimer and higher order array formation remains unclear. Furthermore, molecular mechanisms of signal transduction that are likely to involve inter-dimer interactions are not fully understood. Here we apply all-atom, microsecond-time scale molecular dynamics simulations of the Tsr trimer...
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biorxivpreprint: Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations https://t.co/eSqHDEtAe9 #bioRxiv
biorxiv_biophys: Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations https://t.co/vPKEcIn5Op #biorxiv_biophys
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Authors: 4
Total Words: 7343
Unqiue Words: 2149

2.01 Mikeys
#3. Mechanical Feedback and Robustness of Apical Constrictions in Drosophila Embryo Ventral Furrow Formation
Michael C. Holcomb, Guo-Jie Jason Gao, Mahsa Servati, Dylan Schneider, Presley K. McNeely, Jeffrey H. Thomas, Jerzy Blawzdziewicz
The key process giving rise to ventral furrow formation (VFF) in the Drosophila embryo is apical (outer side) constriction of cells in the ventral region. A combined effect of the cellular constrictions is a negative spontaneous curvature of the cell layer, which buckles inwards. In our recent paper [Gao et al. (2016). J Phys Condens Matter, 28(41), 414021] we showed that the cell constrictions in the initial phase of VFF produce well-de1ned cellular constriction chain (CCC) patterns, and we argued that CCC formation is a signature of mechanical signaling that coordinates apical constrictions through tensile stress. In the present study, we provide a statistical comparison between our active granular 2uid (AGF) model and time lapses of live embryos. We also demonstrate that CCCs can penetrate regions of reduced constriction probability, and we argue that CCC formation increases robustness of VFF to spatial variation of cell contractility.
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biorxivpreprint: Mechanical Feedback and Robustness of Apical Constrictions in Drosophila Embryo Ventral Furrow Formation https://t.co/NhUQJC0Aau #bioRxiv
biorxiv_biophys: Mechanical Feedback and Robustness of Apical Constrictions in Drosophila Embryo Ventral Furrow Formation https://t.co/jeQw2UjmEu #biorxiv_biophys
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Authors: 7
Total Words: 0
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2.01 Mikeys
#4. Antibody-induced crosslinking immobilizes acetylcholine receptors. Mobile receptors exhibit anomalous, cholesterol-sensitive diffusion and clustering.
Alejo Mosqueira, Pablo A. Camino, Francisco J Barrantes
Synaptic strength depends on the number of cell-surface neurotransmitter receptors in dynamic equilibrium with intracellular pools. Dysregulation of this homeostatic balance occurs e.g. in myasthenia gravis, an autoimmune disease characterized by a decrease in the number of postsynaptic nicotinic acetylcholine receptors. Monoclonal antibody mAb35 mimics this effect. Using STORM nanoscopy we characterize the individual and ensemble dynamics of mAb35-crosslinked receptors. Antibody labeling of live cells results in 80% receptor immobilization. The remaining mobile fraction exhibits a heterogeneous combination of Brownian and anomalous diffusion. Single-molecule trajectories exhibit a two-state switching behavior between free Brownian walks and anticorrelated walks within confinement zones. The latter act as permeable fences (~34 nm radius, ~400 ms lifetime). Dynamic clustering, trapping and immobilization also occur in larger areas (~150 nm radius) with longer lifetimes (11 +- 1 s), in a strongly cholesterol-sensitive manner....
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biorxivpreprint: Antibody-induced crosslinking immobilizes acetylcholine receptors. Mobile receptors exhibit anomalous, cholesterol-sensitive diffusion and clustering. https://t.co/5LeyvofhN4 #bioRxiv
biorxiv_biophys: Antibody-induced crosslinking immobilizes acetylcholine receptors. Mobile receptors exhibit anomalous, cholesterol-sensitive ... https://t.co/FGDmp9PEA0 #biorxiv_biophys
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2.003 Mikeys
#5. G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state
Apurba Bhattarai, jinan Wang, Yinglong Miao
G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of ~1/3 of currently marketed drugs. In particular, adenosine A1 receptor (A1AR) is an important therapeutic target for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. As a prototypical GPCR, the A1AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid-protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G protein bound) A1AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A1AR. Our simulations further...
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ramonguixxa: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/1xvehYKflL
Astro_Erik: RT @biorxivpreprint: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/WJv1AQ83rV #bio…
MartaUkleja: RT @biorxiv_biophys: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/SCQ6tA4lPE #bio…
habibhobo: RT @biorxivpreprint: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/WJv1AQ83rV #bio…
midweekwarrior: RT @biorxivpreprint: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/WJv1AQ83rV #bio…
gisellewiggin: RT @ramonguixxa: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/1xvehYKflL
DrPMarimuthu: RT @ramonguixxa: G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state https://t.co/1xvehYKflL
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Authors: 3
Total Words: 8548
Unqiue Words: 2191

2.002 Mikeys
#6. A flexible quantitative phase imaging microscope for label-free imaging of thick biological specimens using aperture masks
Dr Chandrabhan Seniya, Catherine Towers, David Towers
A flexible quantitative phase imaging microscope is reported that offers new capabilities in terms of phase measurement from both thin and thick biological specimens. The method utilises Zernike's phase contrast approach for label-free imaging with a Twymann-Green-based phase-shifting module in the back focal plane. The interfering wavefronts are manipulated by laser-cut apertures to form the scattered and non-scattered fields. The design is flexible enabling a wide range of phase-shifting algorithms to be implemented. Phase maps of the cell membrane, nucleus, and nucleolus of transparent epidermis cells of allium cepa have been examined as proof of concept. The implementation of the phase-shifting module is < 10% of the cost of that using a spatial light modulator whilst delivering an equivalent phase resolution, hence, the microscope scope is very economical.
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biophotonicat: A flexible quantitative phase imaging microscope for label-free imaging of thick biological specimens using aperture masks (relevance: 82%) https://t.co/dZJYGPYSZQ #biophotonics #biomedicaloptics https://t.co/8zvOcxn4mv
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Authors: 3
Total Words: 0
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2.0 Mikeys
#7. Protein folding modulates the adhesion strategy of Gram positive pathogens
Alvaro Alonso-Caballero, Daniel J Echelman, Rafael Tapia-Rojo, Shubhasis Haldar, Edward C Eckels, Julio M. Fernandez
Gram positive bacteria colonize mucosal tissues against large mechanical perturbations, such as coughing, which generate large shear forces that exceed the ability of non-covalent bonds to remain attached. To overcome these challenges, the pathogen Streptococcus pyogenes utilizes the protein Cpa, a pilus tip-end adhesin equipped with a Cys-Gln thioester bond. The reactivity of this bond towards host surface ligands enables covalent anchoring of the bacterium, allowing it to resist large mechanical shocks; however, colonization also requires cell migration and spreading over surfaces. The molecular mechanisms underlying these seemingly incompatible requirements remain unknown. Here, we demonstrate a magnetic tweezers force spectroscopy assay that resolves the dynamics of Cpa thioester bond under force. While folded at forces < 6 pN, Cpa thioester bond reacts reversibly with amine ligands, of common occurrence in inflammation sites; however, mechanical unfolding and exposure to forces higher than 35 pN blocks thioester reactivity...
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cryoET: RT @biorxiv_biophys: Protein folding modulates the adhesion strategy of Gram positive pathogens https://t.co/nfuKakAxnm #biorxiv_biophys
RafaTRojo: RT @biorxiv_biophys: Protein folding modulates the adhesion strategy of Gram positive pathogens https://t.co/nfuKakAxnm #biorxiv_biophys
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Sample Sizes : [259, 49, 2, 12, 9, 4, 19, 8, 4, 8, 3, 165, 20, 15, 12, 8, 9, 7, 12, 5, 7, 10, 3, 4, 24, 21, 19, 21, 165, 21, 117, 12, 11, 7, 7, 5, 4, 3, 42, 13, 58, 12, 12, 8, 5, 11, 11, 5]
Authors: 6
Total Words: 8851
Unqiue Words: 2509

1.998 Mikeys
#8. Mg2+ Impacts the Twister Ribozyme through Push-Pull Stabilization of Non-Sequential Phosphate Pairs
Abhishek Kognole, Alex MacKerell
RNA molecules perform a variety of biological functions for which the correct three-dimensional structure is essential, including as ribozymes where they catalyze chemical reactions. Metal ions, especially Mg2+, neutralize these negatively charged nucleic acids and specifically stabilize RNA tertiary structures as well as impact the folding landscape of RNAs as they assume their tertiary structures. Specific binding sites of Mg2+ in folded conformations of RNA have been studied extensively, however, the full range of interactions of the ion with compact intermediates and unfolded states of RNA is challenging to investigate and the atomic details of the mechanism by which the ion facilitates tertiary structure formation is not fully known. Here, umbrella sampling combined with oscillating chemical potential Grand Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) simulations are used to capture the energetics and atomic-level details of Mg2+-RNA interactions that occur along an unfolding pathway of the Twister ribozyme. The free...
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Authors: 2
Total Words: 12177
Unqiue Words: 2702

1.998 Mikeys
#9. Mesoscale computational protocols for the design of highly cooperative bivalent macromolecules
Suman Saurabh, Francesco Piazza
The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while it is widely accepted that large-scale flexibility (10-100 nm) and free/constrained dynamics (100 ns - mu s) control the activity of such novel molecules, computational strategies at the mesoscale still lag behind experiments in optimizing the design of crucial features, such as the binding cooperativity (a.k.a. avidity). In this study, we introduced different coarse-grained models of a polymer-linked, two-nanobody composite molecule, with the aim of laying down the physical bases of a thorough computational drug design protocol at the mesoscale. We show that the calculation of suitable potentials of mean force allows one to apprehend the nature, range and strength of the thermodynamic forces that govern the motion of free and wall-tethered molecules. Furthermore, we develop a simple...
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Total Words: 12476
Unqiue Words: 2981

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