Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment. Journal Article uri icon



  • 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.

publication date

  • May 31, 2024

has restriction

  • gold

Date in CU Experts

  • May 31, 2024 6:59 AM

Full Author List

  • Skillin NP; Kirkpatrick BE; Herbert KM; Nelson BR; Hach GK; G√ľnay KA; Khan RM; DelRio FW; White TJ; Anseth KS

author count

  • 10

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Additional Document Info

start page

  • eadn0235


  • 10


  • 22