RT Journal Article SR Electronic T1 Spontaneous Phase Separation of Cocultured Cell Mixtures In vitro JF bioRxiv FD Cold Spring Harbor Laboratory SP 152819 DO 10.1101/152819 A1 Sebastian V. Hadjiantoniou A1 Maxime Leblanc-Latour A1 Maxime Ignacio A1 Cory S. Lefevbre A1 Gary W. Slater A1 Andrew E. Pelling YR 2017 UL http://biorxiv.org/content/early/2017/06/20/152819.abstract AB During Embryogenesis, cells undergo constant organizational remodelling. Biochemical and biophysical guidance cues act in tandem to guide migration and morphogenesis into distinct cellular patterns. It has been shown that various cell types will express different configurations of cellular adhesion molecules known as cadherins and integrins. Cocultured in vitro experiments have focused on revealing the extensive genetic expression profiles that modulate embryogenesis whilst overlooking the physical cell-cell and cell-substrate interactions that influence organization. We demonstrate that NIH3T3 and MDCK cells undergo a spontaneous phase separation when cocultured in vitro and that this phenomenon occurs through purely physical binding energies. A Monte Carlo simulation model of a mixture of cells with different cell-cell and cell-substrate binding energies reveals that the spontaneous phase separation occurs due to the minimization of interfacial free energy within the system. Cell-cell and cell-substrate binding plays a critical role in cell organization and is capable of phase separating different populations of cells in vitro.