Mechanical anisotropy and medio-apical force transmission shape cellular strain heterogeneity in epithelia

Mechanical forces play crucial roles in morphogenesis and function, yet individual cells often respond differently to the same external force. Strain heterogeneity, the non-uniform deformation of cells under uniform external mechanical stimuli, may underlie tissue-level robustness and guide morphogenetic outcomes. In this study, we applied a defined uniaxial strain to Xenopus laevis embryonic epithelial explants and investigated how strain was distributed at the single cell level. Our quantitative analysis revealed that cellular strain was heterogeneous, suggesting variable responses to a uniform mechanical stimulus. We found that cell intrinsic material properties, e.g., cell specific mechanical anisotropy had the strongest correlation with strain heterogeneity, suggesting a dominant role in variable mechanical response. We further analyzed how force was distributed at the cellular level using a vinculin force sensor and laser ablation. These experiments demonstrated that forces are primarily transmitted through the medio-apical actin cortex whereas junctional actin facilitates dissipation and remodeling. These findings provide new insights into the physical principles that underlie epithelial resilience and adaptive remodeling, highlighting the importance of distinct functions of junctional and medio-apical actin networks in mechanical adaptation.