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Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices

Research output: Contribution to journalArticlepeer-review

Haguy Wolfenson, Giovanni Meacci, Shuaimin Liu, Matthew Stachowiak, Thomas Iskratsch, Saba Ghassemi, Pere Roca-Cusachs, Ben O'Shaughnessy, James Hone, Michael Sheetz

Original languageEnglish
JournalNature Cell Biology
Volume18
Early online date30 Nov 2015
DOIs
Accepted/In press26 Oct 2015
E-pub ahead of print30 Nov 2015
Published1 Jan 2016

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  • 50099_2_merged_1445337587

    50099_2_merged_1445337587.pdf, 4.33 MB, application/pdf

    Uploaded date:26 Apr 2016

    Version:Accepted author manuscript

King's Authors

Abstract

Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied by local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces by plating cells on sub-micrometre elastomeric pillars. We found that actomyosin-based sarcomere-like contractile units (CUs) simultaneously moved opposing pillars in net steps of ~2.5 nm, independent of rigidity. What correlated with rigidity was the number of steps taken to reach a force level that activated recruitment of α-actinin to the CUs. When we removed actomyosin restriction by depleting tropomyosin 2.1, we observed larger steps and higher forces that resulted in aberrant rigidity sensing and growth of non-transformed cells on soft matrices. Thus, we conclude that tropomyosin 2.1 acts as a suppressor of growth on soft matrices by supporting proper rigidity sensing.

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