PaperPlayer biorxiv biophysics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.25.267195v1?rss=1

Authors: Gagne, D., Azad, R., Edupuganti, U. R., Williams, J., Aramini, J. M., Akasaka, K., Gardner, K. H.

Abstract:

Small molecule binding within internal cavities provides a way to control protein function and structure, as exhibited in numerous natural and artificial settings. Unfortunately, most ways to identify suitable cavities require high-resolution structures a priori and may miss potential cryptic sites. Here we address this limitation via high-pressure solution NMR spectroscopy, taking advantage of the distinctive nonlinear pressure-induced chemical shift changes observed in proteins containing internal cavities and voids. We developed a method to rapidly characterize such nonlinearity among backbone 1H and 15N amide signals without needing to have sequence-specific chemical shift assignments, taking advantage of routinely available 15N-labeled samples, instrumentation, and 2D 1H/15N HSQC experiments. From such data, we find a strong correlation in the site-to-site variability in such nonlinearity with the total void volume within proteins, providing insights useful for prioritizing domains for ligand binding and indicating mode-of-action among such protein/ligand systems. We suggest that this approach provides a rapid and useful way to rapidly assess otherwise hidden dynamic architectures of protein that reflect fundamental properties associated with ligand binding and control.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.25.266163v1?rss=1

Authors: Loveless, J., Garner, A., Issa, A. R., Webb, B., Ohyama, T., Alonso, C.

Abstract:

All animal movement must ultimately be governed by physical laws. As a basis for understanding the interactions between the nervous system, musculature, body mechanics and the environment that govern behaviour in the fruit fly larva, we here develop an effective theory for the physics of its motion in three dimensions. We start by defining a set of fields which quantify stretching, bending and twisting along the larva's anteroposterior (AP) axis. We then perform a search in the space of possible physical theories that could govern these fields, by using symmetry considerations, stability requirements and physical reasoning to rule out possible terms in our theory's Lagrangian (which governs its energy-conservative physics) and Rayleigh function (which governs its energy-dissipative physics). We restrict attention to the physics that dominates at long-wavelengths, which allows us to arrive at a unique, simple theory of the larval midline, governed by a minimum of phenomenological parameters that capture both purely biomechanical as well as neuromuscular effects. Owing to the simplicity of our theory, we are able to derive most of our results analytically. The model makes strong quantitative predictions for the dynamics of peristalsis, rolling, and self-righting, and also successfully predicts statistical properties of these behaviours and of unbiased substrate exploration.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.24.265082v1?rss=1

Authors: Smith, J., Zadeh Haghighi, H., Simon, C.

Abstract:

Understanding the mechanisms underlying anesthesia would be a key step towards understanding consciousness. The process of xenon-induced general anesthesia has been shown to involve electron transfer, and the potency of xenon as a general anesthetic exhibits isotopic dependence. We propose that these observations can be explained by a mechanism in which the xenon nuclear spin influences the recombination dynamics of a naturally occurring radical pair of electrons. We develop a simple model inspired by the body of work on the radical-pair mechanism in cryptochrome in the context of avian magnetoreception, and we show that our model can reproduce the observed isotopic dependence of the general anesthetic potency of xenon in mice. Our results are consistent with the idea that radical pairs of electrons with entangled spins could be important for consciousness.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.25.266387v1?rss=1

Authors: Thiele, J. C., Helmerich, D., Oleksiievets, N., Tsukanov, R., Butkevich, E., Sauer, M., Nevskyi, O., Enderlein, J.

Abstract:

Fluorescence lifetime imaging microscopy (FLIM) is an important technique that adds another dimension to the intensity and colour information of conventional microscopy. In particular, it allows for multiplexing fluorescent labels that have otherwise similar spectral properties. Currently, the only super-resolution technique that is capable of recording super-resolved images with lifetime information is STimulated Emission Depletion (STED) microscopy. In contrast, all Single-Molecule Localisation Microscopy (SMLM) techniques that employ wide-field cameras completely lack the lifetime dimension. Here, we combine Fluorescence-Lifetime Confocal Laser-Scanning Microscopy (FL-CLSM) with SMLM for realising single-molecule localisation-based fluorescence-lifetime super-resolution imaging (FL-SMLM). Besides yielding images with a spatial resolution much beyond the diffraction limit, it determines the fluorescence lifetime of all localised molecules. We validate our technique by applying it to direct STochastic Optical Reconstruction Microscopy (dSTORM) and Points Accumulation for Imaging in Nanoscale Topography (PAINT) im-aging of fixed cells, and we demonstrate its multiplexing capability on samples with two different labels that differ only by fluorescence lifetime but not by their spectral properties

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.24.264655v1?rss=1

Authors: Zhang, Y., Xu, B., Weiner, B. G., Meir, Y., Wingreen, N. S.

Abstract:

Cells possess a multiplicity of non-membrane bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon -- for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.23.263590v1?rss=1

Authors: Gisonno, R. A., Tricerri, M. A., Gonzalez, M. C., Garda, H. A., Ramella, N. A., Diaz Ludovico, I.

Abstract:

We suggest that the structural flexibility is key for certain proteins in order to fulfill functions that are required to interact with biological membranes, and that intra-chain chemical crosslinking may result in a different arrangement of protein with lipids. As interaction with biological membranes and lipids is a function attributed to many proteins in circulation, we intended to characterize an experimental design that helps in the study of many biological protein structures and their function. But in addition, by introducing intra-chain crosslinking, we obtained discoidal nano platforms that are stable under different conditions of temperate and time incubation. These platforms might be an excellent model to employ as biological carriers of intrinsic or external molecules. Thus, data shown here clearly strengthen the usefulness of an easy, accessible and inexpensive tool not only to study protein-lipid interactions, but to be used in different biological fields that require the transport of organic compounds.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.24.264440v1?rss=1

Authors: Malyshev, D., Dahlberg, T., Wiklund, K., Andersson, P. O., Henriksson, S., Andersson, M.

Abstract:

Contamination of toxic spore-forming bacteria is problematic since spores can survive a plethora of disinfection chemicals. It is also problematic to rapidly detect if the disinfection chemical was active, leaving spores dead. Robust decontamination strategies, as well as reliable detection methods to identify dead from viable spores, are thus critical. Vibrational detection methods such as Raman spectroscopy has been suggested for rapid diagnostics and differentiation of live and dead spores. We investigate in this work, using laser tweezers Raman spectroscopy, the changes in Raman spectra of Bacillus thuringiensis spores treated with sporicidal agents such as chlorine dioxide, peracetic acid, and sodium hypochlorite. We also imaged treated spores using SEM and TEM to verify if any changes to the spore structure can be correlated to the Raman spectra. We found that chlorine dioxide did not change the Raman spectrum or the spore structure; peracetic acid shows a time-dependent decrease in the characteristic DNA/DPA peaks and 20 % of the spores were degraded and collapsed; spores treated with sodium hypochlorite show an abrupt drop in DNA and DPA peaks within 20 minutes all though the spore structure was overall intact, however, the exosporium layer was reduced. Structural changes appeared over several minutes, compared to the inactivation time of the spores, which is less than a minute. We conclude that vibrational spectroscopy provides powerful means to detect changes in spores but it might be problematic to identify if spores are live or dead after a decontamination procedure.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.24.264226v1?rss=1

Authors: Guclu, T. F., Kocatug, N., Atilgan, A. R., ATILGAN, C.

Abstract:

PDZ domains constitute common models to study single domain allostery without significant structural changes. The third PDZ domain of PSD-95 (PDZ3) is known to have selective structural features that confer unique modulatory roles to this unit. In this model system two residues, H372 directly connected to the binding site and G330 holding an off-binding-site position, were designated to assess the effect of mutations on binding selectivity. It has been observed that the H372A and G330T/H372A mutations change ligand preferences from class I (T/S amino acid at position -2 of the ligand) to class II (hydrophobic amino acid at the same position). Alternatively, the G330T single mutation leads to the recognition of both ligand classes. We have performed a series of molecular dynamics (MD) simulations for wild-type, H372A, G330T single mutants and a double mutant of PDZ3 in the absence and presence of both types of ligands. With the combination of free energy difference calculations and a detailed analysis of MD trajectories, "class switching" and "class bridging" behavior of PDZ3 mutants, as well as their effects on ligand selection and binding affinities are explained. We show that the dynamics of the charged N-terminus plays a fundamental role in determining the binding preferences in PDZ3 by altering the electrostatic energy. These findings are corroborated by simulations on N-termini truncated versions of these systems. The dynamical allostery orchestrated by the N-terminus offers a fresh perspective to the study of communication pathways in proteins.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.22.262451v1?rss=1

Authors: Kang, J., Koehler, R. C., Adams, S., Graham, E. M., Boctor, E. M.

Abstract:

We present a light-emitting diode (LED)-based transcranial photoacoustic measurement (LED-trPA) of oxyhemoglobin (HbO2) saturation at superior sagittal sinus (SSS) in hypoxic neonatal piglets. The optimal LED imaging wavelengths and frame averaging scheme were determined based on in vivo characterization of transcranial sensitivity. Based on the framework (690/850 nm with >20 frame averaging), graded hypoxia was successfully identified in neonatal piglets in vivo with less than 10.0 % of root mean squared error (RMSE). This preclinical study suggests the feasibility of a rapid, cost-effective, and safe LED-trPA monitoring of perinatal hypoxia-ischemia and prompt interventions for clinical use.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.23.263368v1?rss=1

Authors: Sinha, S., Thirumalai, D.

Abstract:

A single solid tumor, composed of nearly identical cells, exhibits heterogeneous dynamics. Cells dynamics in the core is glass-like whereas those in the periphery undergo diffusive or super-diffusive behavior. Quantification of heterogeneity using the mean square displacement or the self-intermediate scattering function, which involves averaging over the cell population, hides the complexity of the collective movement. Using the t-distributed stochastic neighbor embedding (t-SNE), a popular unsupervised machine learning dimensionality reduction technique, we show that the phase space structure of an evolving colony of cells, driven by cell division and apoptosis, partitions into nearly disjoint sets composed principally of core and periphery cells. The non-equilibrium phase separation is driven by the differences in the persistence of self-generated active forces induced by cell division. Extensive heterogeneity revealed by t-SNE paves way towards understanding the origins of intratumor heterogeneity using experimental imaging data.

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