Confined Water Organization in the Fluid Phase of Phospholipid Self-Assemblies: The Three-Water Layer Model.

Phospholipid-based self-assemblies are frequently studied in cell membrane research and are used in numerous medical and biotechnological applications. Despite current extensive knowledge on membrane nanostructure and its mechanical properties under various environmental conditions, there is still a lack of understanding on interfacial lipid-water interactions. In this chapter, the nature of the confined water is described in the light of the recently proposed Three-Water Layer (TWL) model, discerning (i) 'headgroup water', (ii) 'perturbed water' near the membrane/water interface, and (iii) a core region of 'free', unperturbed water. The interaction of water with lipid leaflets in all three regions is examined in relation to factors such as headgroup type and orientation, membrane rigidity, temperature, ion concentration, and membrane curvature. Notably, the thickness of the perturbed water layer increases with temperature and membrane fluidity, whereas the thickness of the free water core exhibits the opposite trend. Finally, the TWL model is discussed in the context of spectroscopic observations of water within soft confinement, highlighting how varying water dynamics affect the interacting forces between adjacent membranes.