Role of matrix stiffness and stress relaxation on mechanotransduction of HaCaT cells

Abstract

Understanding mechanotransduction appears as an important step in numerous fields of biology, such as cancer, regenerative medicine and tissue engineering. Among the various mechanotransducers, matrix elasticity has been considered as universal regulator of cell behavior. Though, the number of materials that have been investigated is quite small. However, this concept has been recently re-evaluated in the context of other matrix properties such as matrix poroelasticity and stress relaxation along with matrix elasticity. Keeping this in mind here we have investigated the effect of stress relaxation along with matrix elasticity on cell behavior using Polydimethyl siloxane (PDMS) material. For this purpose PDMS matrix of different elasticity and stress relaxation properties (within physiological range) were prepared by varying the base: crosslinker ratio and the effect of the aforesaid physical properties on HaCaT cell physiology were investigated. The study includes cytoskeletal reorganization, proliferation, cell cycle regulation and nuclear mechanotransduction. PDMS matrices were found to have no effect on cell spreading, proliferation and cell cycle regulation of HaCaT cells. The results were further confirmed by checking the expression of FAK-ERK using immunocytochemistry and flow cytometry. However, the variation in matrix stiffness and stress relaxation in case of PDMS matrices were found to be capable of inducing nuclear mechanotransduction as evident from Lamin A/C expression profile. The study showed expression of Lamin A/C varied inversely with PDMS matrix stiffness but maintains a direct proportionality with stress relaxation. It is evident from the study that the concept of matrix stiffness induced mechanotransduction needs to be investigated in more details.