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Differential cellular contractility as a mechanism for stiffness sensing

Dunlop, Carina (2019) Differential cellular contractility as a mechanism for stiffness sensing New Journal of Physics, 21, 063005. pp. 1-9.

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The ability of cells to sense and respond to the mechanical properties of their environments is fundamental to a range of cellular behaviours, with substrate stiffness increasingly being found to be a key signalling factor. Although active contractility of the cytoskeleton is clearly necessary for stiffness sensing in cells, the physical mechanisms connecting contractility with mechanosensing and molecular conformational change are not well understood. Here we present a contractility-driven mechanism for linking changes in substrate stiffness with internal conformational changes. Cellular contractility is often assumed to imply an associated compressive strain. We show, however, that where the contractility is non-uniform, localized areas of internal stretch can be generated as stiffer substrates are encountered. This suggests a physical mechanism for the stretch-activation of mechanotransductive molecules on stiffer substrates. Importantly, the areas of internal stretch occur deep within the cell and not near the cellular perimeter, which region is more traditionally associated with stiffness sensing through e.g. focal adhesions. This supports recent experimental results on whole-cell mechanically-driven mechanotransduction. Considering cellular shape we show that aspect ratio acts as an additional control parameter, so that the onset of positive strain moves to higher stiffness values in elliptical cells.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Mathematics
Authors :
Date : 5 June 2019
Funders : Engineering and Physical Sciences Research Council (EPSRC)
DOI : 10.1088/1367-2630/ab210a
Copyright Disclaimer : © 2019 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft. Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
Depositing User : Clive Harris
Date Deposited : 28 May 2019 09:05
Last Modified : 02 Oct 2019 08:06

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