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

TY - JOUR

T1 - Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices

AU - Wolfenson, Haguy

AU - Meacci, Giovanni

AU - Liu, Shuaimin

AU - Stachowiak, Matthew

AU - Iskratsch, Thomas

AU - Ghassemi, Saba

AU - Roca-Cusachs, Pere

AU - O'Shaughnessy, Ben

AU - Hone, James

AU - Sheetz, Michael

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

U2 - 10.1038/ncb3277

DO - 10.1038/ncb3277

M3 - Article

SN - 1465-7392

VL - 18

JO - Nature Cell Biology

JF - Nature Cell Biology

ER -