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Updated: Oct 1, 2026

Using Solution NMR to Characterize Biomolecular Condensates Under Biphasic Conditions
Published on: April 17, 2026
The thermodynamic state map of biomolecular condensates
Yaoyao Hou1, Lingyun Jing2, Kan Sun2
1Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Abstract:
Biomolecular condensates spatiotemporally regulate cellular biochemistry through liquid-liquid phase separation. In this Perspective, we refine the Condensate Code as a testable thermodynamic state map that integrates continuous cellular inputs, intrinsic molecular grammar and boundary conditions to govern measurable material states. Building on stickers-and-spacers and related grammar frameworks, we highlight a continuum from electrostatic coacervates to viscoelastic networks. We define active anti-grammar as an operational umbrella for localized repulsive or hydration-promoting effects that can counterbalance excessive cohesion when embedded in, modified within or recruited to dense phases. This view predicts measurable changes in partitioning, FRAP recovery, viscosity, aging and fibril-nucleation kinetics. Disruption of the code can drive pathogenic liquid-to-solid transitions and spatial uncoupling with organelle mechanotoxicity. We therefore conceptualize physical therapeutics as programmable macromolecular modulators that test whether localized anti-cohesive effects can remodel pathological material states while monitoring targeting, partitioning, oligomeric intermediates and safety.
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