PaperPlayer biorxiv biophysics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.19.209908v1?rss=1

Authors: Nieves, D. J., Owen, D. M.

Abstract:

Environmentally-sensitive fluorophores report on their local biochemical or biophysical environments through changes in their emission. We combine the solvatochromic probe di-4-ANEPPDHQ with multi-channel SMLM and quantitative analysis of the resulting marked point patterns to map biophysical environments in the mammalian cell membrane. We show that plasma membrane properties can be mapped with nanoscale resolution, and that partitioning between ordered and disordered regions is observed on length scales below 300 nm.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.19.210690v1?rss=1

Authors: Heltberg, M. L., Awada, H. N., Lucchetti, A., Jensen, M. H., Dreyer, J. K., Rasmussen, R.

Abstract:

Parkinsons disease (PD) results from a loss of dopaminergic neurons. The age of disease onset, its progression and symptoms vary significantly between patients, pointing to a complex relationship between neuron loss and PD etiology. Yet, our understanding of the clinical variability remains incomplete. Here, we use biophysical modelling to investigate the dopaminergic landscape in the healthy and denervated striatum. Based on currently proposed mechanisms causing PD, we model three distinct denervation patterns, and show notable differences in the dopaminergic network as denervation progresses. We find local and global differences in the activity of two types of striatal neurons as a function of the denervation pattern. Finally, we identify the optimal cellular strategy for maintaining normal dopamine signaling when neurons degenerate within our model. Our results derive a conceptual framework in which the clinical variability of PD is rooted in distinct denervation patterns and forms testable predictions for future PD research.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.19.205005v1?rss=1

Authors: Wang, Y., Kumar, S., Nisar, A., Bonn, M., Rausch, M. K., Parekh, S. H.

Abstract:

Blood clots are essential biomaterials that prevent blood loss and provide a temporary scaffold for tissue repair. In their function, these materials must be capable of resisting mechanical forces from hemodynamic shear and contractile tension without rupture. Fibrin networks, the primary load-bearing element in blood clots, have unique nonlinear mechanical properties resulting from their hierarchical structure, which provides multiscale load bearing from fiber deformation to protein unfolding. Here, we study the fiber and molecular scale response of fibrin under shear and tensile loads in situ using a combination of fluorescence and vibrational (molecular) microscopy. Imaging protein fiber orientation and molecular vibrations, we find that fiber orientation and molecular changes in fibrin appear at much larger strains under shear compared to uniaxial tension. Orientation levels reached at 150% shear strain were reached already at 60% tensile strain, and molecular unfolding of fibrin was only seen at shear strains above 300%, whereas fibrin unfolding began already at 20% tensile strain. Moreover, shear deformation caused progressive changes in vibrational modes consistent with increased protofibril and fiber packing that were already present even at very low tensile deformation. Together with a bioinformatic analysis of the fibrinogen primary structure, we propose a scheme for the molecular response of fibrin from low to high deformation, which may relate to the teleological origin of its resistance to shear and tensile forces.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/205005v1_ufig1.gif" ALT="Figure 1">

View larger version (21K):

[email protected]@10bed75org.highwire.dtl.DTLVardef@12d33aorg.highwire.dtl.DTLVardef@1e9b40f_HPS_FORMAT_FIGEXP M_FIG C_FIG

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.18.209858v1?rss=1

Authors: Wu, Z., Newstead, S., Biggin, P. C.

Abstract:

The endoplasmic reticulum (ER) is the main site of protein synthesis in eukaryotic cells and requires a high concentration of luminal chaperones to function. During protein synthesis, ER luminal chaperones are swept along the secretory pathway and must be retrieved to maintain cell viability. ER protein retrieval is achieved by the KDEL receptor, which recognises a C-terminal Lys-Asp-Glu-Leu (KDEL) sequence. Recognition of ER proteins by the KDEL receptor is pH dependent, with binding occurring under acidic conditions in the Golgi and release under conditions of higher pH in the ER. Recent crystal structures of the KDEL receptor in the apo and peptide bound state suggested that peptide binding drives the formation of a short-hydrogen bond that locks the KDEL sequence in the receptor and activates the receptor for COPI binding in the cytoplasm. Using quantum mechanical calculations we demonstrate that the strength of this short hydrogen bond is reinforced following protonation of a nearby histidine, linking receptor protonation to high affinity peptide binding. Protonation also controls the wetting of a cavity adjacent to the peptide binding site, leading to a conformational change that ultimately allows the complex to be recognized by the COPI system.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.16.207183v1?rss=1

Authors: Tiffner, A., Schober, R., Hoeglinger, C., Bonhenry, D., Pandey, S., Lunz, V., Sallinger, m., Frischauf, I., Fahrner, M., Lindinger, S., Maltan, L., Berlansky, S., Stadlbauer, M., Schindl, R., Ettrich, R., Romanin, C., Derler, I.

Abstract:

The initial activation step in gating of ubiquitously expressed Orai1 Calcium (Ca2+) ion channels represents the store-dependent coupling to the Ca2+ sensor protein STIM1. An array of constitutively active Orai1 mutants gave rise to the hypothesis that STIM1 mediated Orai1 pore opening is accompanied by a global conformational change of all Orai TM helices within the channel complex. Here, we prove that a local conformational change spreads omnidirectionally within the Orai1 complex. Our results demonstrate that a global, opening-permissive allosteric communication of TM helices is indispensable for pore opening and requires clearance of a series of Orai1 gating checkpoints. We discovered these gating checkpoints in middle and cytosolic extended TM domain regions. Our findings are based on a library of double point mutants that contain each one loss-of-function (LoF) with one gain-of-function (GoF) point mutation in a series of possible combinations. We demonstrated that an array of LoF mutations act dominant over most GoF mutations within the same as well as of an adjacent Orai subunit. We further established inter- and intramolecular salt-bridge interactions of Orai subunits as a core element of an opening-permissive Orai channel architecture. Collectively, clearance and synergistic action of all these gating checkpoints is required to allow STIM1 coupling and Orai1 pore opening.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/207183v2_ufig1.gif" ALT="Figure 1">

View larger version (76K):

[email protected]@1b0ed80org.highwire.dtl.DTLVardef@b89031org.highwire.dtl.DTLVardef@102a53c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.17.206516v1?rss=1

Authors: Zehner, J. S., Royne, A., Sikorski, P.

Abstract:

Microbial-induced calcium carbonate precipitation (MICP) is a biological process inducing bio-mineralization of CaCO3, which can be used to form a solid, concrete-like material. To be able to use MICP successfully for engineering purposes, it is important to understand the formation of the material at the micro-scale to control CaCO3 crystallization. In this contribution we present a systematic study investigating the influence of calcite seeds on the CaCO3 crystallization in MICP. The pH changes during the crystallization process have been monitored in real time with absorption spectroscopy in small volumes, and the optical density (OD) signal was used to analyze the precipitation process. Furthermore, microscopy was used to visualize the precipitation processes in the sample and connect them to changes in pH and OD. We show that there is a significant difference in the pH evolution between samples with and without calcite seeds present and that the shape of the pH evolution and the changes in OD can give valuable information about the precipitation process.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.17.207415v1?rss=1

Authors: Weirich, K. L., Stam, S., Munro, E., Gardel, M. L.

Abstract:

The actin cytoskeleton is a soft, structural material that underlies biological processes such as cell division, motility, and cargo transport. The cross-linked actin filaments self-organize into a myriad of architectures, from disordered meshworks to ordered bundles, which are hypothesized to control the actomyosin force generation that regulates cell migration, shape, and adhesion. Here, we use fluorescence microscopy and simulations to investigate how actin bundle architectures with varying polarity, spacing, and rigidity impact myosin II dynamics and force generation. Microscopy reveals that mixed polarity bundles formed by rigid cross-linkers support slow, bidirectional myosin II filament motion, punctuated by periods of stalled motion. Simulations reveal that these locations of stalled myosin motion correspond to sustained, high forces in regions of balanced actin filament polarity. By contrast, mixed polarity bundles formed by compliant, large cross-linkers support fast, bidirectional motion with no traps. Simulations indicate that trap duration is directly related to force magnitude, and that the observed increased velocity corresponds to lower forces resulting from both the increased bundle compliance and filament spacing. Our results indicate that the properties of actin structures regulate the dynamics and magnitude of myosin II forces, highlighting the importance of architecture and mechanics in regulating forces in biological materials.

Copy rights belong to original authors. Visit the link for more info