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Phase separation in living membranes

Scott P. Rayermann, Glennis E. Rayermann, Caitlin E. Cornell, Alexey J. Merz, and Sarah L. Keller, 2017, Hallmarks of reversible separation of living, unperturbed cell membranes into two liquid phases, Biophys. J., 113:2425-2432.

For decades, controversy surrounded the question of whether spontaneous lateral mixing of membranes into coexisting liquid phases could organize proteins and liquids on micron scales within unperturbed, living cells. A clear answer hinged on the observation of hallmarks of a reversible phase transition. In this paper, by directly imaging micron-scale membrane domains of yeast vacuoles both in vivo and cell-free, we demonstrated that the domains arise through a phase-separation mechanism. Domains in yeast vacuole membranes are large, have smooth boundaries, and can merge quickly, consistent with fluid phases. Moreover, the domains disappear above a distinct miscibility transition temperature and reappear below it, over multiple heating a cooling cycles. Hence, large-scale membrane organization in living cells under physiologically-relevant conditions can be controlled by tuning a single thermodynamic parameter. This paper exemplifies the collaborative research culture of the University of Washington. Sarah and Alex (a professor in the Department of Biochemistry) were joint corresponding authors; Scott and Glennis were joint first authors. To read more about this work, download out the article that Physics Today wrote about our discovery, or check out Alex's tweetorial.

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