Biomolecular Phase Separation: From Molecular Driving Forces to Macroscopic Properties

2020/04/20 by Gregory L. Dignon, Robert B. Best, Jeetain Mittal · 738 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Biology #Biomolecule #Biophysics #Chemical physics #Chemistry #Lipid metabolism and biosynthesis #Materials science #Molecular dynamics #Nanotechnology #Phase (matter) #RNA Research and Splicing #RNA modifications and cancer

paper · pdf · doi:10.1146/annurev-physchem-071819-113553

published in Annual Review of Physical Chemistry 71(1), 53-75 (Annual Reviews)

openalex publication_date 2020/04/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Biological phase separation is known to be important for cellular organization, which has recently been extended to a new class of biomolecules that form liquid-like droplets coexisting with the surrounding cellular or extracellular environment. These droplets are termed membraneless organelles, as they lack a dividing lipid membrane, and are formed through liquid-liquid phase separation (LLPS). Elucidating the molecular determinants of phase separation is a critical challenge for the field, as we are still at the early stages of understanding how cells may promote and regulate functions that are driven by LLPS. In this review, we discuss the role that disorder, perturbations to molecular interactions resulting from sequence, posttranslational modifications, and various regulatory stimuli play on protein LLPS, with a particular focus on insights that may be obtained from simulation and theory. We finally discuss how these molecular driving forces alter multicomponent phase separation and selectivity.

Citations

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