**2.6 Photoswitchable cell–cell adhesions controlling cellular function**

Cell–cell adhesions play an important role in many cellular functions, and the adhesions resulting from the optogenetic proteins are no different. Using CarH based homophilic cell–cell adhesions, the spatiotemporal control of migrations was assessed by measuring the rate and the morphology of cells migrating during a wound-healing assay. The spatiotemporal element was carried out by illuminating discrete sections to depolymerize the cell–cell adhesion. Cells with intact CarH adhesions in the dark showed significantly enhanced migratory potential compared to cells illuminated with green light, which dissociate the cell–cell adhesions. This was characterized by cells remaining together and thus migrating as a single cell wall resulting in faster migration. Cells that were illuminated with blue-green light broke away from the migratory front and engaged in random walking resulting in a slower overall migration rate [59].

Additionally, spatiotemporal control of the cell–cell adhesion complex has been shown in experiments where the β-catenin binding domains on E-cadherin and α-catenin have been replaced with the Halo and SNAP tags, respectively. The Halo/ SNAP system incorporates the UV-light photocleavable small molecule Ha-pl-BG, so adhesions can be reversed upon UV illumination. This system was then applied to MDA-MB-468, which do not express endogenous E-cadherin to assess the efficacy of the system. Using the system cell–cell adhesions could only be observed when the cofactor was present and were degraded rapidly under UV-light. To illustrate the spatiotemporal control, A431 cells, with knocked out α-catenin, were labeled with the Halo/SNAP system and cultured overnight to initiate connections between cells. Specific adhesions between cells were then targeted and illuminated with UV-light. Only the targeted connections were degraded leaving the other connections intact.
