Integrin Tension Represents the Directed Differentiation of Mesenchymal Stem Cells via Mechanoadaptation.

Abstract

The mechanism controlling the differentiation of mesenchymal stromal cells (MSCs) to the target cell is vital for their tissue repair. While integrins, physically connected focal adhesion proteins (FAs), cytoskeleton elements, and lamin A are involved, the quantitative roles of integrin tension and mechanoadaptation remain unknown. Here, we applied reversible shearing DNA-based tension probes (RSDTPs) to assess MSCs' integrin tension during spreading after biochemical induction to osteogenesis and chondrogenesis. The mechanical transmitters of paxillin, F-actin, and lamin A to transduce mechanical stress from integrin to the nucleus as well as differentiation of MSCs were assayed to reveal the mechanical adaptation of integrin tension. Integrin tensions of 44 and 5-18 pN were identified as the critical force for osteogenic and chondrogenic differentiations, respectively. To fit this tension difference, MSCs possessed FAs' orientation to align radially along the cell's normal axis in osteogenesis vs tangentially in chondrogenesis. Cytoskeleton F-actin was found to regulate the osteogenesis through altering the upstream integrin tension and FAs' orientation and the downstream lamin A expression but yield less influences on chondrogenesis. In turn, F-actin tended to be less modulated by lamin A and its accompanying changes in FAs and integrin tension than by biochemical induction. Lamin A favored the regulation of osteogenesis through altering the upstream integrin tension and orientations of FAs and F-actin but might play an inhibitory role in chondrogenic differentiation. This work contributes to the understanding of how integrins generate and transmit different magnitudes of forces to jointly regulate cell morphology and mechanical adaptability and to fit the differentiation fate of MSCs.