(19c) Complexity in a Simple Self-Assembling System: Lecithin-Water-Ethanol Mixtures Exhibit a Re-Entrant Phase Transition and a Vesicle-Micelle Transition (VMT) on Heating

We report surprising results for the self-assembly of lecithin (a common phospholipid) in water-ethanol mixtures. Lecithin is known to form vesicles (~ 100 nm diameter) in water. These vesicles can be transformed into small micelles (~ 5 nm diameter) by a variety of destabilizing agents such as single-tailed surfactants and alcohols. In a surfactant-induced vesicle-micelle transition (VMT), vesicles steadily convert to micelles upon adding the surfactant - and in turn, the turbidity of the solution drops monotonically. Conversely, when an alcohol like ethanol is added to lecithin vesicles, we find a new, distinctive pattern in phase behavior as the ethanol fraction f_eth in water is increased. The turbidity first decreases (from f_eth = 0 to 37%), then rises sharply (f_eth = 37 to 50%), and then eventually decreases again (f_eth > 55%). In conjunction with the turbidity rise, the vesicles separate into two phases around f_eth = 50% before a single phase emerges again at higher f_eth — thus, there is a ‘re-entrant’ phase transition from 1-phase to 2-phase and back to 1-phase as a function of f_eth. Vesicles near the phase boundary (~ f_eth = 45%) also show a VMT upon heating. The same patterns are also seen with other alcohols such as methanol and propanol. We ascribe these complex trends to the dual role played by alcohols: (a) firstly, it reduces the propensity for flat lipid bilayers to bend and form closed spherical vesicles; and (b) secondly, it diminishes the tendency of lipids to self-assemble in the solvent mixture. When (a) dominates, the initially unilamellar vesicles grow into multilamellar vesicles (MLVs), which eventually phase-separate. Thereafter, when (b) dominates, the vesicles convert into micelles. Support for our hypothesis comes from scattering (SANS) and microscopy (cryo-TEM). Thus, we have uncovered a general paradigm for lipid self-assembly in solvent mixtures, and this may even have physiological relevance.