Biophysics of Cell-Substrate Interactions Under Shear

Cells adhere to substrates through mechanosensitive focal adhesion complexes. Measurements that probe how cells detach from substrates when they experience an applied force connect molecular-scale aspects of cell adhesion with the biophysical properties of adherent cells. Such forces can be applied through shear devices that flow fluid in a controlled manner across cells. The signaling pathways associated with focal adhesions, in particular those that involve integrins and receptor tyrosine kinases, are complex, receiving mechano-chemical feedback from the sensing of substrate stiffness as well as of external forces. This article reviews the signaling processes involved in mechanosensing and mechanotransduction during cell-substrate interactions, describing the role such signaling plays in cancer metastasis. We examine some recent progress in quantifying the strength of these interactions, describing a novel fluid shear device that allows for the visualization of the cell and its sub-cellular structures under a shear flow. We also summarize related results from a biophysical model for cellular de-adhesion induced by applied forces. Quantifying cell-substrate adhesions under shear should aid in the development ofmechano-diagnostic techniques for diseases in which cell-adhesion is mis-regulated, such as cancers.