Demixing in cell membranes

The lipid membranes that envelop cells and their substructures are less like rubbery balloons and more like thin liquid films. Proteins and other molecules embedded in the membranes can diffuse from place to place. But despite that diffusion, the membranes are compositionally heterogeneous, and they’ve been postulated to contain discrete domains enriched in different molecules.

Biologists and biophysicists have long debated the mechanism responsible for that organization—and, in particular, whether it has anything to do with thermodynamic phase separation, the same physics that drives the demixing of a shaken bottle of vinegar and oil. One reason the problem is so difficult is that the putative domains in most cell membranes are just tens of nanometers across, too small to be imaged dynamically in vivo.

Now Sarah Keller , Alexey Merz , and their colleagues at the University of Washington in Seattle have presented convincing evidence that membrane domains form through phase separation in at least some living cells. The researchers studied the membranes that enclose vacuoles—a type of organelle—inside single-celled budding yeast. The vacuole membranes host micron-sized domains that can be fluorescently labeled and thus easily imaged.

Keller, Merz, and colleagues sought—and found—two telltale hallmarks of phase separation dynamics. First, when a boundary between two domains of the same phase broke, as shown by the arrows in the figure, the surrounding domain boundaries rearranged within seconds to minimize the overall tension. Second, the domains reversibly dissipated and re-formed when the yeast cells were heated above and cooled below a critical mixing temperature of 38 °C.

Synthetic membranes, which are far easier to image and control than those inside living cells, also show clear signs of phase separation. The Seattle researchers’ yeast results instill confidence that the established synthetic models are indeed relevant to biological systems. It remains to be discovered, however, whether membrane domains in other organelles and species are formed by the same mechanism. (S. P. Rayermann et al., Biophys. J. 113, 2425, 2017 .)