THE ROLE OF RTKS IN CELL RIGIDITY SENSING REGULATION

Abstract

Matrix rigidity is an important physical cue in the microenvironment that can cause changes in cell morphology, migration, and differentiation. But the mechanism of how cell tests substrate rigidity is not clear. In a siRNA screen of the human tyrosine kinases, several kinases were found to be required for the cell rigidity sensing. In this thesis, we analyzed cell behavior on submicron pillar arrays at early stage of cell spreading. Fibroblasts formed contraction units (CUs) with a fixed distance during a constant time scale to sense the substrate rigidity. Two kinases, AXL and ROR2, regulate different aspects and associate with different components of this rigidity sensing system. In addition, studies using a special cell line demonstrated that myosin IIA is one of the essential components for this rigidity sensing contractile units’ formation. This myosin II A dependent rigidity sensing process is under EGFR regulation. Thus, our studies revealed novel and specific mechanisms for different receptor tyrosine kinases involvement in the regulation of cell rigidity sensing.