Hydroxy acid conjugation to lipids increases structural and hydrolytic stability.

Contemporary life requires functional polymers and phospholipid-derived compartmentalization. Mutualistic relationships between compartmentalization and polymerization have never been demonstrated in an abiotic scenario. As both the polymerization of hydroxy acids and the primitive cell-like aggregation of short-chain fatty acids are well known, we study cooperative interactions between compartmentalization and polymerization using these two classes of molecules as a model system. To that end, we explore the formation of various hydroxy acid-fatty acid conjugates. All reactions produce two types of condensation products: hydroxy acid oligoesters and lipid-conjugated oligoesters. We find that conjugation of hydroxy acids to fatty acids leads to the reduction of fatty acid critical aggregation concentration by an order of magnitude. Furthermore, hydroxy acid oligomers are protected against hydrolysis only upon conjugation to fatty acids. Our work offers meaningful insights into the role of self-assembly and cooperative chemistry as selective driving forces in lipid-polymer co-evolution.