Cells migrating on two-dimensional (2D) substrates coordinate the formation of focalized substrate adhesions with cycles of cell protrusion and contraction; however, this mechanism may not accurately describe the movement of cells through 3D space. We sought to determine how 2D motility mechanisms adapt to more complex environments by using a microchannel-based approach to subject migrating cells to varying degrees of physical confinement. By simultaneously observing the movement of cells in both unrestricted 2D space and narrow microchannels, we demonstrate that physical confinement in 3D induces a distinctive mode of motility. Cells migrating in 3�m x 10�m microchannels exhibited a loss of dorsoventral polarity and moved at nearly constant velocity with a distinctive 'sliding' motion. Cells undergoing sliding motility did not generate lamellipodia, stress fibers or mature focal adhesions, and were not impeded by inhibitors of Rho GTPases, ROCK, myosin II or myosin light chain kinase. This work describes a distinctly non-mesenchymal mode of locomotion that is induced by confinement in 3D, and emphasizes that actomyosin-independent tumor cell migration may occur in physiological contexts.

Cellular confinement in 3D suppresses focal adhesions and induces actomyosin-independent motility

243rd National Meeting (2012)

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