Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.
Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.
复制标题
硬度各向异性协调细胞上收缩力，驱动长距离肌管-ECM 对齐。
DOI：
10.1101/2023.08.08.552197
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Anseth,KristiS
中科院分区：
文献类型：
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作者：
Skillin,NathanielP;Kirkpatrick,BruceE;Herbert,KatieM;Nelson,BenjaminR;Hach,GraceK;Günay,KemalArda;Khan,RyanM;DelRio,FrankW;White,TimothyJ;Anseth,KristiS
细胞组织成具有适当结构和功能的组织的能力需要跨越长度尺度的增殖、迁移、极化和分化的有效协调。骨骼肌是天生的各向异性，然而，很少有生物材料可以模仿机械各向异性，以确定其对组织图案的影响，而不引入混淆的地形。在这里，我们证明了基板刚度各向异性协调收缩驱动的集体细胞动力学导致C2C12肌管对齐毫米级的距离。当在缺乏拓扑结构的机械各向异性液晶聚合物网络（LCN）上培养时，C2C12成肌细胞集体地在最硬的方向上伸展。细胞协调是通过相互放大细胞ECM动力学融合过程中出现，驱动全球肌管ECM排序。相反，肌管对齐仅限于小的局部域，对相同化学制剂的机械各向同性LCN没有方向偏好。这些发现为设计模拟各向异性微环境的生物材料提供了有价值的见解，并强调了刚度各向异性在组织形态发生中的重要性。
The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.