The universal polyol platform explains the evolution of lipid headgroups and the origin of membrane function

Biological membranes display extraordinary chemical diversity despite being constructed upon relatively conserved hydrophobic frameworks. Across all domains of life, hydrocarbon chains typically consisting of C10–C18 carbon atoms provide the structural basis for spontaneous membrane self-assembly, whereas the remarkable diversity of membrane functions—including hydration, molecular recognition, electrostatic regulation, catalysis, signal transduction, and environmental adaptation—originates primarily from their polar headgroups. However, the evolutionary origin of membrane headgroup diversity remains largely unexplored. Here, we propose the Universal Polyol Platform Hypothesis, which suggests that abiotic carbon chemistry generated a chemically diverse population of polyhydroxylated molecules, including diols, triols, tetritols, pentitols, hexitols, cyclitols, and related compounds, collectively forming a Universal Polyol Pool. We propose that these polyols constituted the ancestral molecular scaffolds of the earliest amphiphiles, functioning directly as membrane headgroups before the emergence of glycolipids, phospholipids, and other modern membrane lipids. Progressive functional diversification through cyclization, glycosylation, sulfation, amination, phosphorylation, and additional chemical modifications subsequently generated the extraordinary diversity of contemporary membrane headgroups. Within this framework, cyclitols represent the stereochemical apex of the Universal Polyol Platform, while borate functions as the first molecular selector through reversible coordination with polyhydroxylated headgroups, promoting stereochemical recognition and dynamic supramolecular organization. We further propose that the earliest membranes were not passive compartments but chemically active interfaces, in which hydrated polyol headgroups mediated hydrogen bonding, reversible ligand exchange, carbohydrate enrichment, and molecular recognition prior to the evolution of enzymes, receptors, metabolism, and genetic information. This hypothesis complements rather than replaces existing origin-of-life models, including the Lipid World, protocell models, the Lipid Divide, and the RNA World, by addressing a more fundamental evolutionary question: the origin and diversification of membrane headgroups. Modern membrane biophysics, structural biology, lipid engineering, and molecular simulations consistently demonstrate that membrane function resides predominantly within the polar headgroup region, supporting the central evolutionary principle proposed here. We conclude that biological membrane evolution is fundamentally the evolutionary diversification of polar headgroups, whereas hydrophobic hydrocarbon chains provided a comparatively conserved structural scaffold for membrane self-assembly. The Universal Polyol Platform offers a unified framework connecting abiotic carbon chemistry with the emergence of chemically active membranes and the subsequent evolution of modern membrane biology.