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Trends Cell Biol. 2016 Jul;26(7):547-558. doi: 10.1016/j.tcb.2016.03.004. Epub 2016 Apr 1.

Phase Separation: Linking Cellular Compartmentalization to Disease.

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Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
Department of Molecular Mechanisms of Disease, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address:


Eukaryotic cells are complex structures capable of coordinating numerous biochemical reactions in space and time. Key to such coordination is the subdivision of intracellular space into functional compartments. Compartmentalization can be achieved by intracellular membranes, which surround organelles and act as physical barriers. In addition, cells have developed sophisticated mechanisms to partition their inner substance in a tightly regulated manner. Recent studies provide compelling evidence that membraneless compartmentalization can be achieved by liquid demixing, a process culminating in liquid-liquid phase separation and the formation of phase boundaries. We discuss how this emerging concept may help in understanding dynamic reorganization of subcellular space and highlight its potential as a framework to explain pathological protein assembly in cancer and neurodegeneration.


intrinsically disordered proteins; liquid demixing; low-complexity domains; neurodegeneration; phase transition; protein assembly and aggregation

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