Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices.
Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices.
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DOI：
10.1038/ncb3277
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发表时间：
2016-01
影响因子：
21.3
通讯作者：
Sheetz MP
中科院分区：
文献类型：
--
作者：
Wolfenson H;Meacci G;Liu S;Stachowiak MR;Iskratsch T;Ghassemi S;Roca-Cusachs P;O'Shaughnessy B;Hone J;Sheetz MP
细胞通过整合素粘附向细胞外基质施加力来测试细胞外基质的刚性。最近的测量表明，这些力是通过局部微米级收缩施加的，但收缩力如何通过刚性调节尚不清楚。在这里，我们通过将细胞电镀在亚微米弹性柱上来对收缩力进行高时间和空间分辨率的跟踪。我们发现基于肌动球蛋白的肌节样收缩单位 (CU) 同时以约 2.5 nm 的净步长移动相对的支柱，与刚性无关。与刚性相关的是达到激活 α-辅肌动蛋白向 CU 募集的力水平所采取的步数。当我们通过消耗原肌球蛋白 2.1 来消除肌动球蛋白限制时，我们观察到更大的步长和更高的力，导致异常的刚性感应和软基质上非转化细胞的生长。因此，我们得出结论，原肌球蛋白 2.1 通过支持适当的刚性传感来充当软基质上生长的抑制剂。
Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied via 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-micron 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.