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Dynamic and mechanosensitive properties of nascent adhesions

Banff International Research Station for Mathematical Innovation and Discovery

Cellular migration is a tightly regulated process that involves actin cytoskeleton, adaptor proteins, and integrin receptors. Forces are transmitted extracellularly through complexes of these molecules called adhesions. We recently developed a biophysical model of nascent adhesions (NA), as co-localized clusters of integrins and adaptor proteins, to understand their dynamics and mechanosensitive properties. The model was then analyzed to characterize the dependence of NA area on biophysical parameters that regulate the number of integrins and adaptor proteins within NA through a mechanosensitive co-aggregation mechanism. Our results revealed that NA formation is triggered beyond a threshold of adaptor protein, integrin, or extracellular ligand densities (listed in a decreasing order of relative influence), that an increase in co-aggregation or reductions in integrin mobility inside NA potentiate their formation, and that stress (rather than adhesion load) is the permissive mechanical parameter which allows for NA-assembly/disassembly via a bistable-switch possessing a hysteresis. These results were then confirmed by performing stochastic simulations of the model. In this talk, I will give an overview of the model and the predictions made in connection with experimental findings.

Mathematics; Biology and other natural sciences; Partial differential equations; Mathematical biology

video/mp4

Author affiliation: McGill University

2019-12-18

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/72842

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/