Stress-Driven Phase Modulation in Asymmetric Membranes

Compositional asymmetry is a defining property of cellular membranes that influences permeability, protein function, cholesterol dynamics, and shape remodeling. This asymmetry generates a stress imbalance between leaflets, producing opposing tensions. A sufficiently large imbalance can compress one leaflet and trigger a fluid-to-gel phase transition, reducing membrane fluidity and sharply increasing bending rigidity. These phenomena raise a question of how membranes respond mechanically before crossing the transition threshold, a regime that remains relevant to biological functions. We address this question using extensive all-atom and coarse-grained molecular dynamics simulations to investigate how stress asymmetry modulates membrane structure and mechanics near the transition point. Using POPE and DLPC bilayers as model systems, we find that moderate asymmetry induces transient gel-like domains that continuously form and dissolve, amplifying membrane undulations and reducing bending rigidity. Beyond the gelation threshold, this trend reverses as the bilayer stiffens, producing a non-monotonic dependence of rigidity on asymmetry. Together, these results demonstrate that differential leaflet stress can drive either softening or stiffening, complementing the effects of molecular composition. Our findings elucidate how cells might exploit the stress-curvature-phase coupling to tune membrane rigidity under near-physiological conditions.