Author:
Cheah Joleen S.,Jacobs Kyle A.,Heinrich Volkmar,Lo Su Hao,Yamada Soichiro
Abstract
The cytoskeleton provides structural integrity to cells and serves as a key component in mechanotransduction. Tensins are thought to provide a force-bearing linkage between integrins and the actin cytoskeleton; yet, direct evidence of tensin’s role in mechanotransduction is lacking. We here report that local force application to epithelial cells using a micrometer-sized needle leads to rapid accumulation of cten (tensin 4), but not tensin 1, along a fibrous intracellular network. Surprisingly, cten-positive fibers are not actin fibers; instead, these fibers are keratin intermediate filaments. The dissociation of cten from tension-free keratin fibers depends on the duration of cell stretch, demonstrating that the external force favors maturation of cten−keratin network interactions over time and that keratin fibers retain remarkable structural memory of a cell’s force-bearing state. These results establish the keratin network as an integral part of force-sensing elements recruiting distinct proteins like cten and suggest the existence of a mechanotransduction pathway via keratin network.
Funder
HHS | NIH | National Institute of Biomedical Imaging and Bioengineering
NSF | ENG | Division of Civil, Mechanical and Manufacturing Innovation
HHS | NIH | National Cancer Institute
HHS | NIH | National Heart, Lung, and Blood Institute
Publisher
Proceedings of the National Academy of Sciences
Cited by
10 articles.
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