RT Journal Article SR Electronic T1 pH-Responsive Phase Separation Dynamics of Intrinsically Disordered Peptides JF bioRxiv FD Cold Spring Harbor Laboratory SP 2025.01.09.632076 DO 10.1101/2025.01.09.632076 A1 Nandy, Manali A1 Ganar, Ketan A. A1 Ippel, Hans A1 Dijkgraaf, Ingrid A1 Deshpande, Siddharth YR 2025 UL http://biorxiv.org/content/early/2025/01/11/2025.01.09.632076.abstract AB Liquid-liquid phase separation of biomolecules is crucial for maintaining the functional organization in biological systems. Intrinsically disordered proteins are particularly prone to form phase-separated condensates in response to various physicochemical triggers. While the effect of ionic strength and temperature on phase separation dynamics have been studied extensively, the influence of pH is less explored. Here, we study a model glycine-rich protein present in the tick bioadhesive, given its capability to undergo phase separation. After confirming its disordered nature through spectroscopy, we investigated its pH dependence and underlying molecular mechanisms. Our findings reveal that pH significantly influences the protein hydrophobicity via ionic residues, driving notable variations in the coacervation behavior (propensity, progression) and in shaping the material properties (viscosity, interfacial activity) of the formed condensates. Given the ubiquitous presence of disordered proteins in biology, this study provides valuable insights about the broad implications of the pH-dependent behavior of intrinsically disordered proteins.Competing Interest StatementThe authors have declared no competing interest.