Substrate stiffness orchestrates epithelial cellular heterogeneity with controlled proliferative pattern via E-cadherin/β-catenin mechanotransduction

Acta Biomaterialia
Bingjie WangYanan Du

Abstract

Epithelial cellular heterogeneity has been observed in pathological tissues with abnormal matrix stiffness and cells cultured on rigid substrates. However, it remains unclear how matrix stiffness influences cellular heterogeneity formation in multi-cellular population. Here, we demonstrated that cellular heterogeneity regulated by substrate stiffness is evident starting from the initial single-cell stage (indicated by cellular Young's modulus and morphology) until the resulting multi-cellular stage (indicated by cellular functions) through distinguished proliferative patterns. Epithelial cells on soft substrate proliferated in a neighbor-dependent manner with stronger E-cadherin expression and more homogeneous E-cadherin/β-catenin localization compared to those on coverslips, which resulted in reduced heterogeneity in downstream cellular functions of the multi-cellular population. In particular, decreased heterogeneity in human embryonic stem cells upon expansion and endodermal induction was achieved on soft substrate. Overall, our work provides new insights on mechanotransduction during epithelial proliferation which regulates the formation of cellular heterogeneity and potentially provides a highly efficient approach to regul...Continue Reading

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Citations

Jan 19, 2018·Journal of Cellular Physiology·Tingting XiaLi Yang
Feb 16, 2021·Advanced Healthcare Materials·Eva Barcelona-EstajeManuel Salmeron-Sanchez
Feb 11, 2022·Langmuir : the ACS Journal of Surfaces and Colloids·Alice Chinghsuan ChangJun Nakanishi

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