For the first time, we are able to control the interaction between two different cell types using visible light. These photoswitchable cell-cell interactions provide unprecedented spatiotemporal control, allowing us to build tissue structures layer by layer. Different photoswitchable interactions offer varying dynamics in cell interactions, which determines whether compact, ball-like assemblies form under thermodynamic control, or loose, snowflake-like assemblies emerge under kinetic control. By utilizing these photoswitchable interactions, we can control how cells self-assemble and self-sort into multicellular structures, mirroring the principles of self-assembly seen in non-living colloids. In doing so, we have established key rules for the bottom-up assembly of tissues from single cells.
The photoregulation of native cell-cell adhesions directly impacts intracellular signaling and cell behavior. In this project, we developed a photoswitchable version of the native cell-cell adhesion molecule E-cadherin, called opto-Ecad, enabling us to study cellular processes during the epithelial-mesenchymal transition, where intercellular adhesions are spatiotemporally controlled. For example, we demonstrated that 3D spheroids composed of cells with initially strong cell-cell adhesions can invade a collagen gel once the adhesions are turned off with light. On the other hand, we found that artificial photoswitchable cell-cell adhesions, which do not directly link to intracellular signaling, are a valuable tool for studying membrane-generated signals. We showed that these artificial adhesions lead to coordinated collective cell migration and even increase the speed of individual cells by enhancing membrane tension. Through this work, we have highlighted the previously overlooked role of membrane signaling and tension in collective cell migration.
