E-cadherin biomaterials reprogram collective cell migration and cell cycling by forcing homeostatic conditions.

Cells attach to the world through either cell-extracellular matrix adhesion or cell-cell adhesion, and traditional biomaterials imitate the matrix for integrin-based adhesion. However, materials incorporating cadherin proteins that mimic cell-cell adhesion offer an alternative to program cell behavior and integrate into living tissues. We investigated how cadherin substrates affect collective cell migration and cell cycling in epithelia. Our approach involved biomaterials with matrix proteins on one-half and E-cadherin proteins on the other, forming a "Janus" interface across which we grew a single sheet of cells. Tissue regions over the matrix side exhibited normal collective dynamics, but an abrupt behavior shift occurred across the Janus boundary onto the E-cadherin side, where cells attached to the substrate via E-cadherin adhesions, resulting in stalled migration and slowing of the cell cycle. E-cadherin surfaces disrupted long-range mechanical coordination and nearly doubled the length of the G0/G1 phase of the cell cycle, linked to the lack of integrin focal adhesions on the E-cadherin surface.