Data rom: Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment

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 significance of stiffness anisotropy
in orchestrating tissue morphogenesis.

细胞形成结构与功能完备的组织的能力，需要在不同长度尺度上对增殖、迁移、极化及分化过程进行有效协调。骨骼肌天生具有各向异性；然而，能模拟机械各向异性以探究其对组织模式形成的影响且不引入干扰性拓扑结构的生物材料却寥寥无几。本文中，我们证实底物刚度各向异性可协调由收缩性驱动的集体细胞动力学，从而使C2C12肌管在毫米尺度范围内实现排列。当在缺乏拓扑结构的机械各向异性液晶聚合物网络（LCNs）上培养时，C2C12成肌细胞会集体向刚度最大的方向极化。细胞协调作用通过融合过程中出现的细胞-细胞外基质（ECM）相互动力学得到增强，推动整体肌管-ECM有序化。相反，在相同化学配方的机械各向同性LCNs上，肌管排列仅局限于无方向偏好的局部小区域。这些发现为设计模拟各向异性微环境的生物材料提供了宝贵见解，并强调了刚度各向异性在调控组织形态发生中的重要性。