Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness.
Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness.
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DOI：
10.1016/j.isci.2022.104721
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发表时间：
2022-08-19
期刊：
影响因子：
5.8
通讯作者：
Radhakrishnan, Ravi
中科院分区：
文献类型：
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作者：
Parihar, Kshitiz;Nukpezah, Jonathan;Iwamoto, Daniel, V;Janmey, Paul A.;Radhakrishnan, Ravi
Biomechanical signals from remodeled extracellular matrix (ECM) promote tumor progression. Here, we show that cell-matrix and cell-cell communication may be inherently linked and tuned through mechanisms of mechanosensitive biogenesis of trafficking vesicles. Pan-cancer analysis of cancer cells' mechanical properties (focusing primarily on cell stiffness) on substrates of varied stiffness and composition elucidated a heterogeneous cellular response to mechanical stimuli. Through machine learning, we identified a fingerprint of cytoskeleton-related proteins that accurately characterize cell stiffness in different ECM conditions. Expression of their respective genes correlates with patient prognosis across different tumor types. The levels of selected cytoskeleton proteins indicated that cortical tension mirrors the increase (or decrease) in cell stiffness with a change in ECM stiffness. A mechanistic biophysical model shows that the tendency for curvature generation by curvature-inducing proteins has an ultrasensitive dependence on cortical tension. This study thus highlights the effect of ECM stiffness, mediated by cortical tension, in modulating vesicle biogenesis. Non-monotonous mapping between ECM stiffness and cell stiffness Set of cytoskeleton proteins characterize cell stiffness in different ECM conditions Selected cytoskeleton genes' expression correlates with patient prognosis Membrane protrusions (vesicles and tubules) formation favored at low cortical tension Immunology; Biophysics; Mathematical biosciences; Biocomputational method; Cancer
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影响因子：
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McMahon, HT
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