Molecular diffusion and binding kinetics are sufficient to explain condensate-like nuclear clustering

SPARK simulations show that condensate-like nuclear clustering of Brd4, Nanog, Sox2, and Bicoid can be reproduced without protein-protein interactions or phase separation.

• Why it matters: Imaging signatures of biomolecular condensates may not uniquely indicate condensation, leaving uncertainty about whether clustering reflects true phase separation or simpler kinetics.
• What they did: SPARK is a computational framework parameterized by genomic context plus molecular diffusion and binding kinetics, generating optical-microscope spatial distributions while excluding higher-order protein-protein interactions or phase separation.
• The result: Varying nuclear concentrations and enhancer binding-site composition yields similar cluster-like spatial distributions from different kinetic combinations, implying imaging-based features cannot uniquely define the mechanism and that condensation is not required for transcription factor occupancy.

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