Ternary lipid membranes—comprising a high-melting species, a low-melting species, and cholesterol—have long served as minimal model systems for studying lipid organization. Despite their ostensible simplicity, they reproduce a surprising range of the complex mixing behavior observed in biological membranes, including fluid-fluid phase coexistence and its associated critical point. A longstanding motivation behind these studies has been the hope that ternary mixtures might help unravel the enduring mystery of lipid rafts. Extensive research on well-controlled model systems has indeed revealed many of the physical principles that govern ternary lipid phase behavior, while complementary discoveries in living cells have added both support and intrigue. Yet the physiological reality remains perplexing.

Recent findings from multiple groups suggest that further progress will likely require addressing a second fundamental feature of biomembranes: their pronounced asymmetry across the two leaflets. This asymmetry is not limited to composition (i.e., the presence of distinct ternary mixtures in each leaflet) but likely extends to mechanical properties as well. There is growing evidence that the two leaflets may experience very different lateral tensions, resulting in a differential stress that strongly influences cholesterol partitioning—arguably one of the central players in membrane organization.

In this talk, I will examine these two intertwined aspects of biomembrane complexity—compositional and mechanical asymmetry—and propose a generic (though not yet very predictive) thermodynamic framework for describing their interplay. I will also present initial coarse-grained simulation results that begin to elucidate the cross-talk between asymmetry and lipid mixing thermodynamics.

If you would like to attend the seminar, please register here.