Effects of Lateral Stress on the Interfacial Water of Biological Membranes

Interfacial water plays a key role in membrane mechanics, yet its response to lateral stress remains poorly understood. Using molecular dynamics simulations, we investigate how lateral stress affects interfacial water in well-defined lipid bilayer model membranes representative of mammalian- and bacterial-like compositions under physiological conditions. At equilibrium, interfacial water forms hydrogen-bonded networks dominated by four-membered motifs bridging neighboring lipid headgroups. Under lateral stress, these motifs remain stable in mammalian model membranes, whereas in bacterial model membranes, stress-induced surface smoothing leads to partial decoupling of interfacial water from the membrane. This stress-dependent response reveals a strong coupling between membrane mechanics and the hydrogen-bond network topology of interfacial water, providing mechanistic insight into how interfacial water modulates membrane resilience. Overall, our results identify interfacial water as an active, stress-responsive contributor to membrane stability, with broad implications for biophysics, medicinal chemistry, and evolution.