The effect of water stress on liquid ordered and liquid disordered phases of the lipid membrane: an atomistic comparison.
Understanding how biological membranes retain integrity under extreme dehydration is vital for explaining anhydrobiotic survival and defining the physicochemical limits of life. Here, we use molecular dynamics simulations to investigate how progressive dehydration (30-2 water molecules per lipid) affects a liquid-disordered (Ld) DPPC/DOPC/cholesterol membrane. Dehydration reduces the area per lipid and membrane thickness, increases acyl-chain ordering, and majorly suppresses membrane lateral diffusion, with trends comparable to those observed in the liquid-ordered (Lo) phases, indicating a largely phase-independent response. The hydrogen-bond analysis shows that the phosphate-associated oxygen atoms retain the strongest and most persistent interactions, maintaining nearly constant free energy of bond disruption and thereby stabilizing the lipid membrane. Overall, both the Ld and Lo lipid membranes rely on localized head group hydration to withstand water loss, offering molecular insight into lipid membrane resilience in anhydrobiosis, extremophile biology, and water-limited environments.