How yeast harness 2D liquid-liquid phase separation to organize proteins and lipids in vacuole membranes

For decades, scientists have argued about how living cell membranes acquire and maintain liquid regions enriched in specific lipid and protein types. Physicists have long observed liquid-liquid demixing in artificial membranes. Clear identification of the same phase transition in a living biological membrane has heretofore been elusive. By directly imaging micron-scale membrane domains of yeast organelles both in vivo and cell-free, we show that the domains reversibly appear and disappear at a distinct miscibility transition temperature and that the domains merge quickly, consistent with fluid phases. Interesting physical phenomena underlie membrane domains. For example, domains are strongly coupled across both membrane faces (with a coupling parameter of ~0.02 kT/nm²). Similarly, liquid-liquid phase separation can occur near a critical point. Membranes behave as 2-dimensional Ising systems with conserved order parameter; and we have measured the membrane’s effective critical dynamic exponent. A third example is that liquid domains coarsen. As expected, domain radius grows as time^1/3.These results have appeared in PRL (2012) and BJ (2013, 2015, and 2017) and Physics Today (2018).