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Structurally governed cell mechanotransduction through multiscale modeling.

ABSTRACT: Mechanotransduction has been divided into mechanotransmission, mechanosensing, and mechanoresponse, although how a cell performs all three functions using the same set of structural components is still highly debated. Here, we bridge the gap between emerging molecular and systems-level understandings of mechanotransduction through a multiscale model linking these three phases. Our model incorporates a discrete network of actin filaments and associated proteins that responds to stretching through geometric relaxation. We assess three potential activating mechanisms at mechanosensitive crosslinks as inputs to a mixture model of molecular release and benchmark each using experimental data of mechanically-induced Rho GTPase FilGAP release from actin-filamin crosslinks. Our results suggest that filamin-FilGAP mechanotransduction response is best explained by a bandpass mechanism favoring release when crosslinking angles fall outside of a specific range. Our model further investigates the difference between ordered versus disordered networks and finds that a more disordered actin network may allow a cell to more finely tune control of molecular release enabling a more robust response.

SUBMITTER: Kang J

PROVIDER: S-EPMC4342557 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Structurally governed cell mechanotransduction through multiscale modeling.

Kang John J Puskar Kathleen M KM Ehrlicher Allen J AJ LeDuc Philip R PR Schwartz Russell S RS

Scientific reports 20150227

Mechanotransduction has been divided into mechanotransmission, mechanosensing, and mechanoresponse, although how a cell performs all three functions using the same set of structural components is still highly debated. Here, we bridge the gap between emerging molecular and systems-level understandings of mechanotransduction through a multiscale model linking these three phases. Our model incorporates a discrete network of actin filaments and associated proteins that responds to stretching through ...[more]

PMID: 25722249

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Dataset Information

Structurally governed cell mechanotransduction through multiscale modeling.

Publications

Structurally governed cell mechanotransduction through multiscale modeling.

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