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Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu
Jonathon A. Ditlev1,2,*
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada
2Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
*Correspondence to:Jonathon A. Ditlev ,
J Mol Cell Biol, Volume 13, Issue 4, April 2021, 319-324,

Liquid‒liquid phase separation (LLPS) of biomolecules has emerged as an important mechanism that contributes to cellular organization. Phase-separated biomolecular condensates, or membrane-less organelles, are compartments composed of specific biomolecules without a surrounding membrane in the nucleus and cytoplasm. LLPS also occurs at membranes, where both lipids and membrane-associated proteins can de-mix to form phase-separated compartments. Investigation of these membrane-associated condensates using in vitro biochemical reconstitution and cell biology has provided key insights into the role of phase separation in membrane domain formation and function. However, these studies have generally been limited by available technology to study LLPS on model membranes and the complex cellular environment that regulates condensate formation, composition, and function. Here, I briefly review our current understanding of membrane-associated condensates, establish why LLPS can be advantageous for certain membrane-associated condensates, and offer a perspective for how these condensates may be studied in the future.