Matrix Elasticity Affects Integrin Expression in Human Umbilical Cord-Derived Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are a powerful cellular alternative for regenerative medicine and tissue engineering applications due to their multipotency. It is becoming increasingly clear that elasticity of extracellular matrix (ECM) has a profound effect on cell phenotype including adhesion, proliferation and differentiation. Integrins are considered to be important mechanoreceptors in mechanotransduction. While numerous studies have focused on α2, β1 and β3 integrin involvement in substrate stiffness-driven commitment of bone marrow MSCs, comparatively little is known about the change of α5β1 integrin expression in human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on substrates of variable stiffness. We plated hUCMSCs on fibronectin coated polyacrylamide hydrogels with elasticity corresponding to Young’s modulus ranging from 3 to 65 kPa. Our results showed that hUCMSCs displayed different morphologies on substrates of varying stiffness. Cells led to branched morphology similar to that of nerve cells when cultured on soft matrices, while cells became more spread and presented polygonal shapes on stiff substrates. Furthermore, hUCMSCs expressed α5 integrin both on soft substrates and stiff substrates, and the expression levels on the two substrates were similar. The total β1 integrin (including both active and inactive) was higher in hUCMSCs grown on the stiff substrate than that of grown on soft substrates, whereas the activated β1 integrin level on stiff substrates was distinctly lower than that of grown on soft substrates. In conclusion, α5β1 integrin expression in hUCMSCs is dependent on matrix elasticity. The results from this study will provide insight into the role of α5β1 integrin in matrix elasticity-regulated morphologies changes of stem cells and have implication for understanding the mechanism of physical induced lineage specification.