PaperPlayer biorxiv biophysics podcast

PaperPlayer biorxiv biophysics

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Audio versions of bioRxiv paper abstracts

647 Episódios

  • PaperPlayer biorxiv biophysics podcast

    Sex Differences in MRI-Based Metrics of Glioma Invasion and Brain Mechanics

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.21.352724v1?rss=1 Authors: Anderies, B. J., Yee, S. F., Jackson, P. R., Rickertsen, C. R., Hawkins-Daarud, A. J., Johnston, S. K., Clark-Swanson, K. R., Hoxworth, J. M., Le, Y., Zhou, Y., Pepin, K. M., Massey, S. C., Hu, L. S., Huston, J. R., Swanson, K. R. Abstract: Gliomas are brain tumors characterized by highly variable growth patterns. Magnetic resonance imaging (MRI) is the cornerstone of glioma diagnosis and management planning. However, glioma features on MRI do not directly correlate with tumor cell distribution. Additionally, there is evidence that glioma tumor characteristics and prognosis are sex-dependent. Magnetic resonance elastography (MRE) is an imaging technique that allows interrogation of tissue stiffness in-vivo and has found utility in the imaging of several cancers. We investigate the relationship between MRI features, MRE features, and growth parameters derived from an established mathematical model of glioma proliferation and invasion. Results suggest that both the relationship between tumor volume and tumor stiffness as well as the relationship between the parameters derived from the mathematical model and tumor stiffness are sex-dependent. These findings lend evidence to a growing body of knowledge about the clinical importance of sex in the context of cancer diagnosis, prognosis and treatment. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    Three-dimensional interrelationship between osteocyte network and forming mineral during human bone remodeling

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.391862v1?rss=1 Authors: Ayoubi, M., van Tol, A. F., Weinkamer, R., Roschger, P., Brugger, P., Berzlanovich, A., Bertinetti, L., Roschger, A., Fratzl, P. Abstract: During bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation were three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). In agreement with previous observations, the mineral concentration was found to gradually increase from the central Haversian canal towards preexisting mineralized bone. Most interestingly, a similar feature was discovered on a length scale more than 100-times smaller, whereby mineral concentration increased from the LCN, leaving around the canaliculi a zone virtually free of mineral, the size of which decreases with progressing mineralization. This suggests that the LCN controls mineral formation but not just by diffusion of mineralization precursors, which would lead to a continuous decrease of mineral concentration from the LCN. Our observation is, however, compatible with the co-diffusion and reaction of precursors and inhibitors from the LCN into the bone matrix. Copy rights belong to original authors. Visit the link for more info
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  • PaperPlayer biorxiv biophysics podcast

    Coarse-grained modeling of mitochondrial metabolism enables subcellular flux inference from fluorescence lifetime imaging microscopy

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.392225v1?rss=1 Authors: Yang, X., Needleman, D. J. Abstract: Mitochondria are central to metabolism and their dysfunctions are associated with many diseases. Metabolic flux, the rate of turnover of molecules through a metabolic pathway, is one of the most important quantities in metabolism, but it remains a challenge to measure spatiotemporal variations in mitochondrial metabolic fluxes in living cells. Fluorescence lifetime imaging microscopy (FLIM) of NADH is a label-free technique that is widely used to characterize the metabolic state of mitochondria in vivo. However, the utility of this technique has been limited by the inability to relate FLIM measurement to the underlying metabolic activities in mitochondria. Here we show that, if properly interpreted, FLIM of NADH can be used to quantitatively measure the flux through a major mitochondrial metabolic pathway, the electron transport chain (ETC), in vivo with subcellular resolution. This result is based on the use of a coarse-grained NADH redox model, which we test in mouse oocytes subject to a wide variety of perturbations by comparing predicted fluxes to direct biochemical measurements and by self-consistency criterion. Using this method, we discovered a subcellular spatial gradient of mitochondrial metabolic flux in mouse oocytes. We showed that this subcellular variation in mitochondrial flux correlates with a corresponding subcellular variation in mitochondrial membrane potential. The developed model, and the resulting procedure for analyzing FLIM of NADH, are valid under nearly all circumstances of biological interest. Thus, this approach is a general procedure to measure metabolic fluxes dynamically in living cells, with subcellular resolution. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    TRPV channel OCR-2 is distributed along C. elegans chemosensory cilia by diffusion in a local interplay with intraflagellar transport

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.390005v1?rss=1 Authors: van Krugten, J., Danne, N., Peterman, E. J. G. Abstract: Sensing and reacting to the environment is essential for survival and procreation of most organisms. Caenorhabditis elegans senses soluble chemicals with transmembrane proteins (TPs) in the cilia of its chemosensory neurons. Development, maintenance and function of these cilia relies on intraflagellar transport (IFT), in which motor proteins transport cargo, including sensory TPs, back and forth along the ciliary axoneme. Here we use live fluorescence imaging to show that IFT machinery and the sensory TP OCR-2 reversibly redistribute along the cilium after exposure to repellant chemicals. To elucidate the underlying mechanisms, we performed single-molecule tracking experiments and found that OCR-2 distribution depends on an intricate interplay between IFT-driven transport, normal diffusion and subdiffusion that depends on the specific location in the cilium. These insights in the role of IFT on the dynamics of cellular signal transduction contribute to a deeper understanding of the regulation of sensory TPs and chemosensing. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.390187v1?rss=1 Authors: Casalino, L., Dommer, A. C., Gaieb, Z., Barros, E. P., Sztain, T., Ahn, S.-H., Trifan, A., Brace, A., Ma, H., Lee, H., Turilli, M., Bogetti, A., Khalid, S., Chong, L., Simmerling, C., Hardy, D., Maia, J., Phillips, J., Kurth, T., Stern, A., Huang, L., McCalpain, J., Tatineni, M., Gibbs, T., Stone, J. E., Jha, S., Ramanathan, A., Amaro, R. E. Abstract: We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike's full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems. Copy rights belong to original authors. Visit the link for more info
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    Adherent cell remodeling on micropatterns is modulated by Piezo1 channels

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.18.389106v1?rss=1 Authors: Jetta, D., Bahrani Fard, M. R., Sachs, F., Munechika, K., Hua, S. Z. Abstract: Adherent cells utilize local environmental cues to make decisions on their growth and movement. We have previously shown that HEK293 cells grown on the fibronectin stripe patterns were elongated. Here we show that Piezo1 function is involved in cell spreading. Inhibiting the Rho-ROCK pathway also reversibly inhibited cell extension indicating that myosin contractility is involved. Piezo1 expressing HEK cells plated on fibronectin stripes elongated, while a knockout of Piezo1 eliminated elongation. Inhibiting Piezo1 conductance using GsMTx4 or Gd3+ blocked cell spreading, but the cells grew thin tail-like extensions along the patterns. Images of GFP-tagged Piezo1 showed plaques of Piezo1 moving to the extrusion edges, co-localized with focal adhesions. Surprisingly, in non-spreading cells Piezo1 was located primarily on the nuclear envelope. The growth of thin extrusion tails did not occur in Piezo1 knockout cells suggesting that Piezo1 may have functions besides acting as a cation channel. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    Optimal density of biological cells

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.18.388744v1?rss=1 Authors: Pang, T. Y., Lercher, M. Abstract: A substantial fraction of the bacterial cytosol is occupied by catalysts and their substrates. While a higher volume density of catalysts and substrates might boost biochemical fluxes, the resulting molecular crowding can slow down diffusion, perturb the reactions' Gibbs free energies, and reduce the catalytic efficiency of proteins. Due to these tradeoffs, dry mass density likely possesses an optimum that facilitates maximal cellular growth and that is interdependent on the cytosolic molecule size distribution. Here, we analyse the balanced growth of a model cell with metabolic and ribosomal reactions, accounting systematically for crowding effects on reaction kinetics. We find that changes in cytosolic density affect biochemical efficiency more strongly for ribosomal reactions than for metabolic reactions, which involve much smaller catalysts and reactants. Accordingly, optimal cytosolic density depends on cellular resource allocation into ribosomal vs. metabolic reactions. A shift in the relative contributions of these sectors to the cellular economy explains the 10% difference in the cytosolic density between E. coli bacteria growing in nutrient-rich and -poor environments. We conclude that cytosolic density variation in E. coli is consistent with an optimality principle of cellular efficiency. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    Biological autoluminescence for assessing oxidative processes in yeast cell cultures

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.388801v1?rss=1 Authors: Vahalova, P., Cervinkova, K., Cifra, M. Abstract: Nowadays, modern medicine is looking for new, more gentle and more efficient diagnostic methods. A pathological state of an organism is often closely connected with increased amount of reactive oxygen species (ROS). They can react with biomolecules and subsequent reactions can lead to very low endogenous light emission (biological autoluminescence - BAL). This phenomenon can be potentially used as a non-invasive and low-operation-cost tool for monitoring oxidative stress during diseases. To contribute to the understanding of the parameters affecting BAL, we analyzed the BAL from yeast Saccharomyces cerevisiae as a representative eukaryotic organism, The relationship between the BAL intensity and amount of ROS that originates as a result of the Fenton reaction as well as the correlation between spontaneous BAL and selected physical and chemical parameters (pH, oxygen concentration, and cell concentration) during cell growth were established. Copy rights belong to original authors. Visit the link for more info
  • PaperPlayer biorxiv biophysics podcast

    The role of alpha-helix on the structure-targeting drug design of amyloidogenic proteins

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.391409v1?rss=1 Authors: Tempra, C., La Rosa, C., Lolicato, F. Abstract: The most accredited hypothesis links the toxicity of amyloid proteins to their harmful effects on membrane integrity through the formation of prefibrillar-transient oligomers able to disrupt cell membranes. However, damage mechanisms necessarily assume a first step in which the amyloidogenic protein transfers from the aqueous phase to the membrane hydrophobic core. This determinant step is still poorly understood. However, according to our lipid-chaperon hypothesis, free lipids in solution play a crucial role in facilitating this footfall. Free phospholipid concentration in the aqueous phase acts as a switch between ion channel-like pore and fibril formation, so that high free lipid concentration in solution promotes pore and repress fibril formation. Conversely, low free lipids in the solution favor fibril and repress pore formation. This behavior is due to the formation of stable lipid-protein complexes. Here, we hypothesize that the helix propensity is a fundamental requirement to fulfill the lipid-chaperon model. The alpha-helix region seems to be responsible for the binding with amphiphilic molecules fostering the proposed mechanism. Indeed, our results show the dependency of protein-lipid binding from the helical structure presence. When the helix content is substantially lower than the wild type, the contact probability decreases. Instead, if the helix is broadening, the contact probability increases. Our findings open a new perspective for in silico screening of secondary structure-targeting drugs of amyloidogenic proteins. Copy rights belong to original authors. Visit the link for more info
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    How a Hemicarcerand Incarcerates Guests at Room Temperature Decoded with Modular Simulations

    Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.390328v1?rss=1 Authors: McFerrin, K. G., Pang, Y.-P. Abstract: Hemicarcerands are host molecules created to study constrictive binding with guest molecules for insights into the rules of molecular complexation. However, the molecular dynamics simulations that facilitate such studies have been limited because three-dimensional models of hemicarcerands are tedious to build and their atomic charges are complicated to derive. There have been no molecular dynamics simulations of the reported water-soluble hemicarcerand (Octacid4) that explain how it uniquely encapsulates its guests at 298 K and keeps them encapsulated at 298 K in NMR experiments. Herein we report a modular approach to hemicarcerand simulations that simplifies the model building and charge derivation in a manner reminiscent of the approach to protein simulations with truncated amino acids as building blocks. We also report that apo Octacid4 in water adopts two clusters of conformations, one of which has an equatorial portal open thus allowing guests to enter the cavity of Octacid4, in microsecond molecular dynamics simulations performed using the modular approach at 298 K. Under the same simulation conditions, the guest-bound Octacid4 adopts one cluster of conformations with all equatorial portals closed thus keeping the guests incarcerated. These results explain the unique constrictive binding of Octacid4 and suggest that the guest-induced host conformational change that impedes decomplexation is a previously unrecognized conformational characteristic that promotes strong molecular complexation. Copy rights belong to original authors. Visit the link for more info

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