Molecular dynamics perspectives on annexin-mediated plasma membrane repair: From recruitment to membrane mechanics.

This mini-review examines how molecular dynamics simulations reshape the view of annexin-mediated plasma membrane repair from simple recruitment to coupled protein-membrane states. Molecular dynamics simulations show that annexin-induced curvature is shaped by oligomerization, cholesterol, and anionic lipid chemistry, while engineering normally non-trimerizing annexin A3 into a trimer-forming state demonstrates that curvature generation alone does not ensure repair competence. Membrane-active perturbants such as trifluoperazine further suppress repair by altering bilayer thickness, lipid packing, phosphatidylserine mobility, and annexin binding. These findings shift the question from whether annexins arrive to how protein-membrane states generate repair-relevant remodeling.