ArticleSmall (Weinheim an der Bergstrasse, Germany)2026
Topology-Encoded Charge Polarity Governs Multiphase Organization in Intrinsically Disordered Protein Polymer Condensates.
Article in Small (Weinheim an der Bergstrasse, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Synthetic biomolecular condensates offer a route to engineer compartmentalized microenvironments with tunable physicochemical properties, yet design principles for controlling their internal organization remain limited. Here, we report a minimal two-component system based on thermoresponsive intrinsically disordered protein polymers with lower critical solution temperature behavior (LCST-IDPPs), in which electrostatic topology programs liquid-liquid phase separation (LLPS). Incorporating charged residues into LCST-IDPPs suppresses phase separation under physiological conditions, whereas mixing oppositely charged, individually non-coacervating IDPPs restores LLPS as an emergent, composition-dependent process driven by multivalent intermolecular charge compensation. We compare this two-component system with a covalently linked diblock containing the same charged chains. This change in chain connectivity alters the coupling between electrostatic pairing, counterion redistribution, and LCST-driven dehydration. As a result, the balance between inter- and intrachain ionic pairing encodes the residual charge and micropolarity of the dense phase. This topology-dependent microenvironment controls condensate miscibility and drives the formation of either homogeneous or internally demixed multiphase assemblies. The condensate interior also shifts the apparent pK
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