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. 2022 Oct 3;10:953590. doi: 10.3389/fbioe.2022.953590

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Copyright © 2022 Yang, Zhang, Tan and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Impact of substrate stiffness. (A) Schematic representation of the main changes in substrate stiffness and their effects on the corneal epithelium. The central region is stiffer than the peripheral region in both the corneal epithelium and stroma, and the anterior stroma is stiffer than the posterior stroma. Stiffer substrates promote differentiation of limbal epithelial stem cells (LESCs), while softer substrates promote the proliferation process. (B) Substrate stiffness affects the behavior of LESCs via the YAP-dependent mechanotransduction pathway with involvement of ΔNp63 and β-catenin. (C) Substrate stiffness and chemical factors influence the behaviors of keratocytes. Softer substrates inhibit proliferation of keratocytes and migration of fibroblasts. Softer substrates also preserve the phenotype of keratocytes, while stiffer substrate promotes keratocyte–fibroblast–myofibroblast (KFM) transformation induced by transforming growth factor-β1 (TGF-β1). This stiffness-related transformation could be suppressed by histone deacetylase inhibitors, hepatocyte growth factor, and latrunculin B. Furthermore, extracellular matrix (ECM) stiffness also affects the response of fibroblasts to fibroblast growth factor (FGF) by the interplay between Rho and Rac signaling.