Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments.
Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments.
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DOI：
10.1083/jcb.200405004
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发表时间：
2004-09-13
期刊：
影响因子：
--
通讯作者：
Discher DE
中科院分区：
文献类型：
--
作者：
Engler AJ;Griffin MA;Sen S;Bönnemann CG;Sweeney HL;Discher DE
收缩性肌细胞提供了一个假设的测试，即细胞感觉到它们的机械以及分子微环境，相应地改变表达，组织和/或形态。在这里，成肌细胞被培养在附着在不同弹性的玻璃或聚合物凝胶上的胶原条上。随后融合成肌管的发生与底物的柔韧性无关。然而，肌球蛋白/肌动蛋白条纹只出现在具有正常肌肉典型硬度的凝胶上（被动杨氏模量，E = 12 kPa）。在玻璃和更软或更硬的凝胶上，包括模拟僵硬的营养不良肌肉的凝胶，细胞不成条纹。此外，生长在玻璃附着肌管（但不是较软的成纤维细胞）的顺应性底层顶部的肌管将产生条纹，而底部细胞将仅组装应力纤维和富含粘着斑蛋白的粘附。与肌节形成不同，粘附强度相对于基底硬度单调增加，在玻璃上具有最强的粘附力。这些发现对在体内将干细胞引入改变机械组成的患病或受损横纹肌具有重要意义。
Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here, myoblasts were cultured on collagen strips attached to glass or polymer gels of varied elasticity. Subsequent fusion into myotubes occurs independent of substrate flexibility. However, myosin/actin striations emerge later only on gels with stiffness typical of normal muscle (passive Young's modulus, E ∼12 kPa). On glass and much softer or stiffer gels, including gels emulating stiff dystrophic muscle, cells do not striate. In addition, myotubes grown on top of a compliant bottom layer of glass-attached myotubes (but not softer fibroblasts) will striate, whereas the bottom cells will only assemble stress fibers and vinculin-rich adhesions. Unlike sarcomere formation, adhesion strength increases monotonically versus substrate stiffness with strongest adhesion on glass. These findings have major implications for in vivo introduction of stem cells into diseased or damaged striated muscle of altered mechanical composition.
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