Benny Geiger's Lab

(In collaboration with Prof. Alexander Bershadsky, Department of Molecular Cell Biology)

Cell elongation and polarization are basic morphogenetic responses to extracellular matrix adhesion. We demonstrated that human cultured fibroblasts readily polarize when plated on rigid, but not on compliant, substrates. On rigid surfaces, large and uniformly oriented focal adhesions (FAs) form, while cells plated on compliant substrates form numerous small and radially oriented adhesions. Live-cell monitoring during cell spreading indicated that FA alignment precedes the overall elongation of the cell, suggesting that FA orientation might direct cell polarization. siRNA-mediated knockdown of 85 human protein tyrosine kinases (PTKs) induced distinct alterations in the cell polarization response, as well as diverse changes in FA organization. Remarkably, changes in focal adhesion mechanosensing were consistently accompanied by corresponding changes in the cell polarization response. We propose that the different stages of rigidity-dependent cell polarization are regulated via multiple, PTK-dependent molecular checkpoints that, in concert, control FA-mediated mechanosensing.

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