α-catenin switches between a slip and an asymmetric catch bond with F-actin to cooperatively regulate cell junction fluidity

By using laser tweezers, the authors show that a single alpha-catenin molecule does not resist force on F-actin. However, clustering of multiple molecules and force applied toward F-actin pointed end engage a molecular switch in alpha-catenin, which unfolds and strongly binds F-actin. alpha-catenin is a crucial protein at cell junctions that provides connection between the actin cytoskeleton and the cell membrane. At adherens junctions (AJs), alpha-catenin forms heterodimers with beta-catenin that are believed to resist force on F-actin. Outside AJs, alpha-catenin forms homodimers that regulates F-actin organization and directly connect the cell membrane to the actin cytoskeleton, but their mechanosensitive properties are inherently unknown. By using ultra-fast laser tweezers we found that a single alpha-beta-catenin heterodimer does not resist force but instead slips along F-actin in the direction of force. Conversely, the action of 5 to 10 alpha-beta-catenin heterodimers together with force applied toward F-actin pointed end engaged a molecular switch in alpha-catenin, which unfolded and strongly bound F-actin as a cooperative catch bond. Similarly, an alpha-catenin homodimer formed an asymmetric catch bond with F-actin triggered by protein unfolding under force. Our data suggest that alpha-catenin clustering together with intracellular tension engage a fluid-to-solid phase transition at the membrane-cytoskeleton interface.