Micromechanical control of cell-cell interactions

The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By using a micromachined silicon substrate with moving parts, we demonstrate the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micrometer-scale precision. We thereby achieve mechanical control of both tissue composition and spatial organization. As a case study, we demonstrate the utility of this tool in deconstructing the dynamics of intercellular communication between hepatocytes and supportive stromal cells in coculture. Our findings indicate that the maintenance of the hepatocellular phenotype by stroma requires direct contact for a limited time (approximate to hours) followed by a sustained soluble signal that has an effective range of <400 mu m. This platform enables investigation of dynamic cell-cell interaction in a multitude of applications, spanning embryogenesis, homeostasis, and pathogenic processes.