Using Force to Probe Bipolar Activation of Integrins and Signaling at Cell Surfaces
Using an ultrasensitive force probe and basic statistical principles, we have developed a novel method to assay both the kinetic rates at which adhesive ligands dissociate from cell receptors and the rates at which the receptors separate from the cytoskeleton in the course of single molecule pulling experiments. Using results from probe tests of ICAM-1 bonds to L 2 integrin on leukocytes, I will show that cell signaling not only regulates lifetimes and strengths of the outer-ligand adhesive bond but also lifetimes and strengths of cohesive integrin anchoring to the cell cytostructure. Whether triggered from outside or inside the cell, the results indicate that the mechanical linkage between integrin tail domains and the cytoskeleton is a key effector of integrin activation in cell signaling (e.g. analogous to the “mechanical transmission” in an automobile).