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For decades, scientists have argued about the mechanisms of how living cell membranes acquire regions enriched in particular lipid and protein types. One highly contested theory has been that domains form via phase separation, as occurs in simple artificial membranes. This theory has been slow to gain acceptance because it contradicts the widespread assumption that inhomogeneities in living cell membranes are limited to sub-micron sizes (whereas phase separation results in much larger domains). Since the 1960s, researchers have reported tantalizing hints that membranes in yeast do indeed phase separate. However, proof of phase separation hinges on observation of a reversible phase transition. Here, we provide that direct evidence for vacuole membranes of living yeast cells. Inversely, when might unusually small domains appear in artificial membranes? Current theories of membrane microemulsions and modulated phases present several firm hypotheses, which we test in simple vesicle systems. In our system, small, stable domains are only observed in membranes with excess area. Host: Michael Wall |