Micropolarity governs the structural organization of biomolecular condensates.

Abstract

Membraneless organelles within cells have unique microenvironments that play a critical role in their functions. However, how microenvironments of biomolecular condensates affect their structure and function remains unknown. In this study, we investigated the micropolarity and microviscosity of model biomolecular condensates by fluorescence lifetime imaging coupling with environmentally sensitive fluorophores. Using both in vitro and in cellulo systems, we demonstrated that sufficient micropolarity difference is key to forming multilayered condensates, where the shells present more polar microenvironments than the cores. Furthermore, micropolarity changes were shown to be accompanied by conversions of the layered structures. Decreased micropolarities of the granular components, accompanied by the increased micropolarities of the dense fibrillar components, result in the relocation of different nucleolus subcompartments in transcription-stalled conditions. Our results demonstrate the central role of the previously overlooked micropolarity in the regulation of structures and functions of membraneless organelles.