The Control Centers of Biomolecular Phase Separation: How Membrane Surfaces, PTMs, and Active Processes Regulate Condensation

Mol Cell. 2019 Oct 17;76(2):295-305. doi: 10.1016/j.molcel.2019.09.016. Epub 2019 Oct 8.


Biomolecular condensation is emerging as an essential process for cellular compartmentalization. The formation of biomolecular condensates can be driven by liquid-liquid phase separation, which arises from weak, multivalent interactions among proteins and nucleic acids. A substantial body of recent work has revealed that diverse cellular processes rely on biomolecular condensation and that aberrant phase separation may cause disease. Many proteins display an intrinsic propensity to undergo phase separation. However, the mechanisms by which cells regulate phase separation to build functional condensates at the appropriate time and location are only beginning to be understood. Here, we review three key cellular mechanisms that enable the control of biomolecular phase separation: membrane surfaces, post-translational modifications, and active processes. We discuss how these mechanisms may function in concert to provide robust control over biomolecular condensates and suggest new research avenues that will elucidate how cells build and maintain these key centers of cellular compartmentalization.

Keywords: biomolecular condensates; membranes; molecular chaperones; phase separation; post-translational modifications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Compartmentation*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Endocytosis
  • Humans
  • Intracellular Membranes / metabolism
  • Molecular Chaperones / metabolism
  • Nucleic Acid Conformation
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism*
  • Protein Conformation
  • Protein Processing, Post-Translational*
  • Protein Transport*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Solubility
  • Structure-Activity Relationship


  • Molecular Chaperones
  • Nucleic Acids
  • Proteins