Configurational entropy is the driving force of ethanol action on membrane architecture.

A colligative thermodynamic framework is developed to describe the action of ethanol on membranes. The partitioning of ethanol into a membrane structure imparts a randomness, configurational entropy, that stabilizes that structure from an energetic standpoint. When partitioning between membrane structures differs, the equilibrium between them is altered to favor the structure with the largest partition coefficient for ethanol. The action of ethanol and temperature originate in entropy and are equated through entropy. Membrane equilibria that are predicted to be most sensitive to the action of ethanol (where dilute concentrations of ethanol cause a perturbation equal to a large change in temperature) are those that exhibit a small thermal entropy change and a large difference in solute partitioning between membrane structures. Our model predicts that ethanol does not act on a single membrane structure, but on both structures in an equilibrium. The thermodynamic framework is applied to the action of ethanol on cooperative equilibria in a dipalmitoyl lecithin model membrane. Ethanol-induced perturbations are monitored by electron paramagnetic resonance (EPR) using the spin label, Tempo. The equilibrium between the gel and ripple-structures (L beta'-->P beta', pretransition) exhibits a small change in thermal entropy and, as predicted, is more sensitive to the action of ethanol than the equilibrium between the ripple and fluid bilayer-structures (P beta'-->L alpha, main transition) which exhibits a large thermal entropy change. The framework suggests that ethanol acts through entropy, as does temperature, thereby upsetting the natural thermal balance that maintains membrane architecture.