Adenosine 5’-triphosphate (ATP) forms protein-free and responsive condensates in crowded environments

Abstract Adenosine 5’-triphosphate (ATP) is found to form biomolecular condensates with proteins. However, without complementary proteins, the small size and high charge density of ATP molecules create substantial electrostatic and entropic barriers that prevent them from forming condensates. Here, we find that macromolecular crowding overcomes these energetic barriers, promoting ATP molecules to self-associate and form protein-free liquid-like condensates through screened electrostatic repulsion and enhanced hydrogen bonding. Importantly, ATP condensates are responsive to multiple stimuli and create distinct microenvironments that selectively enrich various guest molecules and protect ribonucleic acids from DNAzyme cleavage. These findings uncover important roles of ATP in forming dynamic, chemically distinct condensates via homotypic interactions, potentially expanding its classical view beyond a canonical energy carrier to a structural and regulatory architect in cellular physiology and prebiotic chemistry. Competing Interest Statement Ho Cheung Shum is a scientific advisor of EN Technology Limited, MicroDiagnostics Limited, PharmaEase Tech Limited, Upgrade Biopolymers Limited and Multera Limited, in which he owns some equity, and is a founding director and co-director of the research center, Advanced Biomedical Instrumentation Centre Limited. The works in this paper are, however, not directly related to the works of these entities, as far as we know. The authors declare no other competing interests.