Role of zwitterionic lipid headgroups on monolayer formation and interfacial dilatational rheology in binary mixtures of phospholipids and cholesterol: A pendant drop tensiometer study

The complex composition of biological membranes, comprising a diverse array of lipids with unique moieties, has garnered increased attention due to the recognized roles of lipids in membrane stability and biological processes. Even subtle changes in phospholipid headgroups and fatty acyl tails profoundly affect the formation and interfacial dynamics of lipid monolayers at the air-water interface. However, the molecular-level understanding of their intermolecular forces and interactions during these processes, directly relating to the lipid chemical structures, is not well-explored. To better understand these complex physicochemical phenomena, simplified model monolayers with precise control over lipid types and compositions are utilized. In this study, we employ the pendant drop tensiometer technique to investigate the formation and interfacial rheology of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) monolayers, with varying amounts of cholesterol (CHOL) for the first time. These two phospholipids, with identical C16:0 acyl tails but different headgroups, exhibit marked differences in their interfacial interactions with CHOL and water molecules, consequently affecting monolayer formation and rheology. In the absence of CHOL, DPPE monolayers typically display a lower dilatational modulus than DPPC, attributed to increased headgroup hydration. However, introducing CHOL reverses this trend, resulting in stiffer DPPE-CHOL monolayers compared to DPPC-CHOL. With CHOL, we observe its well-known condensation effect on DPPC monolayers, yet for DPPE monolayers, both condensation and expansion effects are noted, contingent on CHOL amount. We anticipate this work will not only deepen our fundamental understanding of the structure-composition-property relationships in lipid molecules but also provide a robust foundation for comprehending more intricate biological systems.