Do membranes in intact cells undergo macroscopic lipid domain phase separation

Ascertain whether macroscopic phase separation of lipid domains into distinct phases (such as lipid-ordered and lipid-disordered domains) occurs in intact biological cell membranes, and, if so, characterize the conditions and signatures of such separation in vivo.

Background

Model membrane studies show macroscopic phase separation into ordered and disordered lipid domains, often used as an analogue for lipid rafts and membrane compartmentalization. However, intact cellular membranes are active, crowded, and coupled to the cytoskeleton and cytoplasm, complicating direct extrapolation from in vitro systems.

Recent perspectives suggest that criticality or near-critical fluctuations may underlie observed membrane heterogeneities in cells, leaving open whether true macroscopic phase separation occurs in vivo. Resolving this requires discriminating critical fluctuations from bona fide phase-separated domains in living membranes.