Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

56-POS Board 56 MT1-MMP Regulates Focal Adhesion Turnover and Cellular Traction Stresses Yukako Nishimura 1 , Sergey V. Plotnikov 2 , Pakorn Kanchanawong 1 , Alexander D. Bershadsky 1,3 . 1 Mechanobiology Institute, Singapore, Singapore, 2 University of Toronto, Toronto, ON, Canada, 3 Weizmann Institute of Science, Rehovot, Israel. Focal adhesions are cellular organelles serving as the mechanical linkages between the cell and the extracellular matrix (ECM). Cells need to control turnover of focal adhesions spatiotemporally for directed migration. In addition, focal adhesions have been shown to be sites for the ECM degradation by matrix metalloproteases (MMPs), key enzymes essential for directed cell migration and tumor-cell invasion. The mechanisms of cross-talk between focal adhesions and MMPs remain, however, poorly understood. Here, we have identified a role of MT1-MMP, one of the major trans-membrane MMPs, in the turnover of focal adhesion. Knockdown of MT1-MMP resulted in increase of focal adhesion size and slowing down their disassembly rate as compared to the focal adhesions in control cells. To test if MT1-MMP affects force exerted by cells on the substrate, we used traction force microscopy. We showed that MT1- MMP knockdown cells developed higher traction stresses than control cells. Live imaging of MT1-MMP has revealed that this enzyme is localized to vesicle-like structures, moving along microtubules and frequently fusing with the plasma membrane in proximity of the focal adhesions visualized by paxillin labeling. Tracking the MT1-MMP vesicles during focal adhesion disassembly revealed a tight spatio-temporal correlation between frequency of MT1- MMP vesicles fusion with the plasma membrane and the disassembly of focal adhesions. Taken together, these data suggest that MT1-MMP is trafficked by microtubules towards focal adhesions and then controls focal adhesions dynamics, as well as mechanical tension applied by focal adhesions to the ECM.

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