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

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

Research output: Contribution to journalArticle

82 Scopus citations

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 of1/42.5 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.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
JournalNature Cell Biology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Cell Biology

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    Wolfenson, H., Meacci, G., Liu, S., Stachowiak, M. R., Iskratsch, T., Ghassemi, S., Roca-Cusachs, P., O'Shaughnessy, B., Hone, J., & Sheetz, M. P. (2016). Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices. Nature Cell Biology, 18(1), 33-42. https://doi.org/10.1038/ncb3277