Adhesion-contractile balance in myocyte differentiation

Adhesion-contractile balance in myocyte differentiation
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DOI:
10.1242/jcs.01496
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发表时间:
2004-11-15
影响因子:
4
通讯作者:
Discher, DE
Discher, DE
中科院分区:
生物学2区
文献类型:
--
作者:
Griffin, MA;Sen, S;Discher, DE

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组织细胞通常拉动其基质附着物并平衡准静态收缩性与充分粘附,但与表型的任何相关性和/或对表型的影响尚不清楚。在这里,我们开始,以证明如何分化状态夫妇肌动球蛋白为基础的收缩,通过粘附和基板的遵守。肌管与胶原图案盖玻片上的成肌细胞分化,其允许线性融合但防止经典的肌管分支。融合后,肌管粘附在微条上,但锁定在富含应力纤维的状态,并且不进一步显著分化。相比之下,生长在这些细胞上的肌管确实通过分化而进展,在一周内表现出肌动球蛋白条纹。一个顺应性的粘附到这些较低的细胞建议耦合到收缩性和适应上层细胞条纹所需的重组。通过机械分离肌管的一端来评估这些贴壁细胞的收缩性。所有的肌管,无论是否有条纹,都以指数衰减缩短。细胞对细胞肌管放松更多,这意味着更大的收缩应力。非肌肉肌球蛋白II抑制剂blebbistatin可抑制上述两种情况下的松弛。因此,在文化中的肌管明显预应力肌球蛋白II,这种收缩性夫妇基板的依从性,并最终影响肌动球蛋白条纹。
Tissue cells generally pull on their matrix attachments and balance a quasi-static contractility against adequate adhesion, but any correlation with and/or influence on phenotype are not yet understood. Here, we begin to demonstrate how differentiation state couples to actomyosin-based contractility through adhesion and substrate compliance. Myotubes are differentiated from myoblasts on collagen-patterned coverslips that allow linear fusion but prevent classic myotube branching. Post-fusion, myotubes adhere to the micro-strips but lock into a stress fiber-rich state and do not differentiate significantly further. In contrast, myotubes grown on top of such cells do progress through differentiation, exhibiting actomyosin striations within one week. A compliant adhesion to these lower cells is suggested to couple to contractility and accommodate the reorganization needed for upper cell striation. Contractility is assessed in these adherent cells by mechanically detaching one end of the myotubes. All myotubes, whether striated or not, shorten with an exponential decay. The cell-on-cell myotubes relax more, which implies a greater contractile stress. The non-muscle myosin II inhibitor blebbistatin inhibits relaxation for either case. Myotubes in culture are thus clearly prestressed by myosin II, and this contractility couples to substrate compliance and ultimately influences actomyosin striation.