Understanding the regulatory mechanism of compression-induced mechanopodia in human mesenchymal stem cells

Abstract

Mechanical signal is an important factor that can affect cell fate but the mechanism on how cells respond and adapt to mechanical loadingis not well understood. Our previous study has reported the formation of mechanoresponsive, omni-directional and local matrix-degrading actin protrusions, termed mechanopodia, in human mesenchymal stem cells (hMSCs) microencapsulated in collagen upon cyclic compression in order to understand their unique identity and the signaling mechanism behind the formation of these protrusions. While it is still unknown whether they are different from other major types of actin protrusions (such as filopodia, podosomes, invadopodia) on the cell surface membrane, mechanopodia differ in terms of the stability, abundance and major molecular markers. Understanding the signaling mechanism regulating the formation of these mechanopodia is essential. It’s been known that small GTPases of the Rho subfamily such as Cdc42 and Rac1 regulate the formation of actin filaments. This study aims to reveal the dependence of mechanopodia formation on Cdc42 and Rac1 signaling. The inhibition of Cdc42 by incubating the hMSCs in ML141 did not prevent the formation of the mechanopodia, while Rac1 inhibition with NSC23766 resulted in a drastic change in morphology with the apparent absence of mechanopodia. This suggests that mechanopodia formation may indeed be dependent on the presence of Rac1but not on Cdc42. More in-depth analyses are needed to confirm the signaling regulation of mechanopodia and to reveal their functional and physiological significance.