Identification of cell migratory cues by control of microenvironmental adhesion

Directed cell migration is central to embryonic development, tissue homeostasis, and disease progression. However, regulation of cell migration is notoriously difficult to study. Although past experiments have shown purified extracellular matrix (ECM) proteins can direct cell migration, whether multiple ECMs can guide cell migration remains unknown. Here, I simultaneously pattern multiple ECMs via a simple extension of microcontact printing. Through this method, I find a continuous cell-ECM adhesion can be composed of distinct types of integrins segregated to different ECMs, and that cells can migrate directionally on an ensemble of ECMs just as well as they can on single ECMs. Together, these data directly suggest that integrins coordinately regulate cell migration. How cell-cell adhesion impinges on cell migration is elusive. But using micropatterned substrates to engineer cell-cell adhesion, I found that cell-cell adhesion triggered cell polarization, which is the first step of cell migration, and required E-cadherin, Cdc42 activity, and the actin cytoskeleton to do so. Very little is known about how cell-cell collisions might alter migration, despite an early description of such ‘contact inhibition of locomotion’ and its prominence in embryonic development and cancer. The current knowledge deficit is due largely to the lack of experimental platforms with which to study cell-cell collisions. I describe robust contact inhibition of locomotion via a facile experimental platform and suggest via computational simulations that synchronized polarization emerges from the context of contact inhibition of locomotion. Together, these studies illustrate not only experimental methodologies to engineer adhesion, but also uncover novel regulation of cell migration