Phase-separated condensates modulate light absorption of small molecules and the application for drug analysis

Phase-separated condensates selectively enrich a wide range of molecules and regulate their properties, playing essential roles in cellular functions and pathological processes. While their regulatory effects on macromolecules have been extensively studied, the effects on small molecules remain less understood. This study carefully investigates how peptide condensates affect the light absorption properties across twelve small-molecule dyes. By controlling the formation and removal of the condensates, it is observed that the dyes exhibit diverse changes in light absorption, depending on their enrichment state and location within the condensates. This phenomenon is attributed to the combined physiochemical properties of the condensates, including the spatial confinement and the chemical microenvironment. Based on this finding, a simple spectral method is developed for the analysis of the condensate-small molecule interaction. This approach is further applied to an antitumor drug, demonstrating its general applicability. This study uncovers the fundamental phenomenon that biomolecular condensates modulate the light absorption of small molecules, providing implications for pharmacodynamics and broader biomedical research.