Small Molecules Influence the Physical Microenvironment of Biomolecular Condensates

作者：Yifei Pan, Jun Lei, Shiqi Mou, Zhili Wu, Longchen Zhu, Liyao Zeng, Feng Luo, Yaping Ding, Yu Liu, Xin Zhang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c04180 · 被引用次数：17 · 研究领域：RNA Research and Splicing、RNA modifications and cancer、Heat shock proteins research

Biomolecular condensates exhibit distinct microenvironments that arise from interactions between proteins, RNA, and solutions. In aqueous solutions, these membraneless structures constantly encounter small molecules that could affect the structure and properties of the condensates. However, the effects of organic small molecules in water solutions on the microenvironments of condensates remain poorly understood. In this study, we used various organic solutes as an example to explore how small molecules could influence the physicochemical properties in the microenvironment of protein condensates. Particularly, we quantitatively studied micropolarity and microviscosity using a combination of techniques, including fluorescence lifetime imaging microscopy, fluorescence recovery after photobleaching, and passive rheology. Unexpectedly, our results revealed that the microenvironment was not correlated with the polarity of organic solutes; instead, the correlation was observed on the interaction strength between water and small molecules. We found that solutes with stronger interaction with water and weaker interaction with proteins increase the micropolarity and decrease the microviscosity of condensates. Furthermore, we demonstrated that the modulation of the micropolarity of condensates could impact the miscibility of multicomponent condensates. Finally, we showed that organic solutes could influence the micropolarity of condensates and the partitioning of products in condensates...