  Cell--cell and cell-matrix adhesions play essential roles in the function of
tissues. There is growing evidence for the importance of crosstalk between
these two adhesion types, yet little is known about the impact of these
interactions on the mechanical coupling of cells to the extracellular-matrix
(ECM). Here, we combine experiment and theory to reveal how intercellular
adhesions modulate forces transmitted to the ECM. In the absence of
cadherin-based adhesions, primary mouse keratinocytes within a colony appear to
act independently, with significant traction forces extending throughout the
colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a
cohesive colony localize traction forces to the colony periphery. Through
genetic or antibody-mediated loss of cadherin expression or function, we show
that cadherin-based adhesions are essential for this mechanical cooperativity.
A minimal physical model in which cell--cell adhesions modulate the physical
cohesion between contractile cells is sufficient to recreate the spatial
rearrangement of traction forces observed experimentally with varying strength
of cadherin-based adhesions. This work defines the importance of cadherin-based
cell--cell adhesions in coordinating mechanical activity of epithelial cells
and has implications for the mechanical regulation of epithelial tissues during
development, homeostasis, and disease.
