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

• Published in: Nature cell biology Vol. 18; no. 1; pp. 33 - 42
• Main Authors: Wolfenson, Haguy, Meacci, Giovanni, Liu, Shuaimin, Stachowiak, Matthew R., Iskratsch, Thomas, Ghassemi, Saba, Roca-Cusachs, Pere, O’Shaughnessy, Ben, Hone, James, Sheetz, Michael P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2016; Nature Publishing Group
• Subjects: 14/10; 14/63; 631/80/79; 631/80/79/2066; Actin Cytoskeleton; Actins - metabolism; Actomyosin - metabolism; Cancer Research; Cell Adhesion; Cell Biology; Cytoskeletal proteins; Developmental Biology; Extracellular matrix; Extracellular Matrix - metabolism; Fibroblasts; Genetic aspects; Humans; Life Sciences; Matriu extracel·lular; Muscle Contraction - physiology; Properties; Rigidity; Sarcomeres - metabolism; Stem Cells; Stress, Mechanical; Tropomyosin - metabolism; United States
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb3277

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.
Sheetz and colleagues use micropillar arrays to report that the regulation of rigidity sensing involves the tropomyosin-dependent control of the stepwise contractions needed to reach a force level sufficient for integrin adhesion reinforcement.