Abstract Water transport across lipid bilayers is a fundamental biological process, but most model systems fail to capture the molecular complexity of biological cell membranes. As a result, the extent to which the membrane composition choreographs its permeability and how it is modulated by small molecules is poorly understood. Here, we use droplet interface bilayers (DIBs) formed using either synthetic 1,2‐dioleoyl‐ sn ‐glycero‐3‐phosphocholine (DOPC) or biologically sourced phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids to examine how lipid biomimicry influences passive water permeability. We also study the effect of two “membrane‐active” molecules: cholesterol, which in our membranes should reduce permeability, and niacin, which has been reported to enhance membrane permeability. We find that biomimetic PC/PE membranes exhibit an approximately eightfold higher baseline water permeability than synthetic DOPC membranes. The presence of cholesterol reduces water permeability in both types of membranes, while niacin has an opposing effect, increasing water permeability in a concentration‐dependent manner. However, only synthetic membranes show full recovery and overshoot of baseline levels of water permeability with the addition of niacin, whereas biomimetic membranes display limited recovery. Our work shows that the use of biologically relevant phospholipid mixtures in model membranes is essential to accurately capture the behavior of the membrane with respect to water permeability.
Forigua et al. (2026) studied this question.