Pierre-François Lenne (@pflenne.bsky.social)

Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. These events involve the remodeling of cell contacts driven by active cytoskeletal contractile forces. However how cell-cell contacts remodel remains poorly understood because of lack of tools to directly apply forces at cell-cell contacts to produce their remodeling. Here we develop a dual-optical trap manipulation method to impose different force patterns on cell-cell contacts in the early epithelium of the Drosophila embryo. Through different push and pull manipulations at the edges of junctions, the technique allows us to produce junction extension and junction shrinkage. We use these observations to constrain and specify vertex-based models of tissue mechanics, incorporating negative and positive mechanosensitive feedback depending on the type of remodeling. We show that Myosin-II activity responds to junction strain rate and facilitates full junction shrinkage. Altogether our work provides insight into how stress produces efficient deformation of cell-cell contacts in vivo and identifies unanticipated mechanosensitive features of their remodeling. Significance statement The highly organized tissues and organs that form our body emerge from internal dynamic activities at the cellular level. Among such activities, cell shape changes and cell rearrangement, cell extrusion and cell division sculpt epithelial tissues into elongated sheets, tubes and spherical cavities. Remodeling of cell-cell contacts, powered by actomyosin contractility, is key to all these transformations. Although much is known about the molecular machinery and biochemical signals that regulate remodeling of cell contacts, there is a lack of approaches to directly probe the mechanics of cell contacts and therefore assess their ability to resist or deform in response to mechanical loads. We developed an experimental technique to manipulate and exert contractile and extensile forces to cell-cell junctions. Our results lead to a specific physical model of junctional mechanics, with implications in the modeling of collective cell behavior in epithelial tissues. ### Competing Interest Statement The authors have declared no competing interest. https://www.biorxiv.org/content/10.1101/2022.07.08.499278v2