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Mechanobiology of Disease
Poster Abstracts
90
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.