Intra- and intermembrane pairwise molecular recognition between synthetic hydrogen-bonding phospholipids.

Multivalency and preorganization are fundamental aspects of molecular recognition at the lipid membrane-water interface and can render weak monomeric binding interactions selective and robust; this concept is important throughout biology, biotechnology, and materials science. Though hydrogen bonding is typically weakened in water, intramembrane hydrogen bonding between native lipids has been well-studied and is thought to contribute to lipid bioactivity and membrane function. We hypothesized that avidity and preorganization effects at the lipid-water interface could overcome solvent competition and allow for selective hydrogen-bond recognition between small, unstructured components. We have found that electrostatically identical vesicular membranes composed of cyanuric acid and melamine functionalized phospholipids 1 and 2 undergo selective apposition, fusion and adhesion in suspension and on solid support, indicating that their well-known low-dielectric hydrogen bonding properties translate effectively to the lipid-water interface. This work is notable and of general interest given the few detailed studies of aqueous phase hydrogen-bonding systems; we have extensively characterized this system, gaining structural, functional, and thermodynamic data. Furthermore, we have found that the designed lipid-lipid headgroup interactions result in dramatic alteration of the lipid phase morphology, providing insight into the coupling of molecular interactions with assembly state. As such, this work contributes to our understanding of fundamental phenomena such as molecular recognition at the lipid-water interface membrane chemistry and further illustrates the general possibility of designing selective hydrogen-bonding adhesive interactions from simple starting materials at other polar-apolar interfaces; this could have numerous materials and biotechnological applications.