Cell Coat Mediated Cell Migration

Abstract

Cell migration depends on a sequence of adhesion and detachment events. These events arise during the cyclic migration process, which involves the integrin-dependent adhesion machinery, the acto-myosin system and the signaling pathways between them. Migration appears to rely on a delicate spatio-temporal regulation of cell adhesion to the surrounding substrate. Studies of cell migration in physiological contexts have shown that a pericellular coat, a thickened polymer matrix attached to many cell surfaces, often is required to facilitate cell migration, including that of aggressively spreading cancers. Cell motility in these systems directly depends on the formation of a large, hyaluronan-rich cell coat with an asymmetric distribution around the polarized migrating cell. Removal or alteration of the coat substantially decreases motility - to the point that such treatments have been proposed as therapies for some types of cancer. The hyaluronan biology community often speculates that cell migration requires the ‘insulation’ and/or the mechanical properties provided by the cell coat. However, little has been done to substantiate this claim. A bigger problem yet is that the lubricating effect of hyaluronan has been shown to oppose adhesion, which leads to a conundrum in the present context: How is it possible that inhibition of adhesion can help a cell migrate, when adhesion is absolutely necessary to gain traction and exert the force to move the cell forward? We have developed a microfluidics-based cell migration assay capable of presenting several surface gradients of fibronectin of different slopes to induce cell migration within the same device. We study the ability of these gradients to induce cell migration and their influence on the cell coat phenotype and mechanical properties using a combination of fluorescent labeling, particle exclusion assays, and optical tweezer force probe experiments.