Phase Coexistence and Domain Formation in Lipid Bilayers

As soon as one considers membranes comprising two lipid species or more, and biological membranes have a very complex composition indeed, one expects the possibility of lipid segregation. On the other hand, it is natural to assemble lipids of complementary physical and chemical properties together in order to design membranes with optimal responsive properties with respect to their environment (light, charge, stress of flow). It is therefore important to properly characterize the different segregated domains and to understand the principles underlying phase coexistence in lipid membranes.

Contributing to the development of new tools to inspect the level of molecular organization in phase separated domains, we have studied coexisting ordered and disordered liquid phases in a ternary giant vesicle, by combining measurements of fluorescence lifetime and polarization in a two- photon geometry. We measure the order parameter of fluorescent probes that segregate selectively into the different domains and correlate probe wobbling degrees of freedom with the degree of cholesterol enrichment [1].

Figure 1: Prism representation of the temperature variation of the ternary phase diagram for a mixture of saturated and unsaturated lipids and cholesterol.

Theoretically, we have recently achieved an important step towards developing a friendly tool for predicting the phase behaviour of binary and ternary mixtures containing cholesterol [2]. Starting from the concept of order parameter that underlies the so-called gel to lipid main transition, we proposed a simple mean- field Gibbs free-energy displaying the most essential features of the ternary saturated/unsaturated/ cholesterol systems. Our model provides the most accurate prediction to date of such a Gibbs ternary phase diagram. Unlike previous attempts, it requires as input only basic knowledge on the single lipids main transition, basic features of the lipid-cholesterol binary coexistence gap and a single additional free parameter. We illustrate the potential of our approach by sketching a scenario for the morphological evolution of ternary phase diagrams with temperature. Work is currently under way to extend the approach to other lipids as well as to more complex situations - quaternary mixtures, non- vanishing surface tension - that can easily be incorporated into the picture. This work will hopefully give birth to a user-friendly web-based interface for predicting the phase behaviour of systems containing arbitrarily chosen lipid species, which is the middle term goal that we aim at.