The peritumoral physical microenvironment consists of complex topographies that influence cell migration. The decision making of cells upon encountering anisotropic, physiologically-relevant physical cues has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysis of cell decision making in a variety of well-defined physical microenvironments. Cell decision making following lateral confinement on 2D microcontact printed lines is governed by the branch width at bifurcations. Cells confined in narrow feeder microchannels also preferentially enter wider branches at bifurcations. In contrast, in feeder channels wider than the cell body, cells elongate along one channel side wall and are contact guided to the contiguous branch channel independently of branch channel width. This contact guidance-mediated decision is regulated by the lateral and axial length scales of the feeder channels. Knockdown of b1-integrins or inhibition of cellular contractility suppresses contact guidance. Concurrent, but not individual, knockdown of non-muscle myosin isoforms IIA and IIB decreases contact guidance, suggesting the existence of a compensatory mechanism between MIIA and MIIB. Conversely, knockdown or inhibition of Cdc42 promotes contact guidance-mediated decision making. Taken together, the dimensionality, length scales of the physical microenvironment and intrinsic cell signaling regulate cell decision making at intersections

Interplay of the physical microenvironment, contact guidance and cell signaling in cell decision making

251st National Meeting (2016)

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