E-cadherin Substrates Alter the Biophysics of Collective Cell Migration and Proliferation

While conventional biomaterials focus on cell-matrix interaction, cell-cell adhesion is a promising, complementary process to target given its significance in tissue integrity, mechanical signaling, and stem cell fate. We investigate this by patterning zones of E-cadherin – a key cell-cell adhesion protein – and collagen on culture surfaces and explore how this 'cell-mimetic' biomaterial influences collective cell behaviors in macro-scale epithelial monolayers. First, we observe nearly 5X slower mean collective cell migration speeds on E-cadherin substrates compared to those on collagen control substrates. Such slower migration can be explained by our data showing that focal adhesions cannot form on cadherin surfaces, in turn altering cytoskeletal architecture. However, pronounced cellular recruitment of E-cadherin is observed at the cell-material interface, which not only stabilizes cell geometry, but extends the cell cycle, specifically resulting in a large increase in G1 transit times, with no effect on the S-G2-M phases. This effect seems to be driven by biomechanical reprogramming of cell size control effectors such as YAP, beta-catenin, and Wnt.