Interplay Between Intracellular Transport Dynamics and Liquid‒Liquid Phase Separation

• Published in: Advanced science 2024-05, Vol.11 (19), p.e2308338-n/a
• Main Authors: Zhang, Ming‐Li, Zhang, Ziheng, Niu, Xue‐Zhi, Ti, Hui‐Ying, Zhou, Yu‐Xuan, Gao, Bo, Li, Yiwei, Liu, Ji‐Long, Chen, Xiaosong, Li, Hui
• Format: Article
• Language: English
• Subjects: Cytoplasm; diffusion; intracellular dynamics; liquid‒liquid phase separation; molecular crowding; Physiology; Proteins; Quantum dots
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202308338

Liquid‒liquid phase separation (LLPS) is a ubiquitous process in which proteins, RNA, and biomolecules assemble into membrane‐less compartments, playing important roles in many biological functions and diseases. The current knowledge on the biophysical and biochemical principles of LLPS is largely from in vitro studies; however, the physiological environment in living cells is complex and not at equilibrium. The characteristics of intracellular dynamics and their roles in physiological LLPS remain to be resolved. Here, by using single‐particle tracking of quantum dots and dynamic monitoring of the formation of stress granules (SGs) in single cells, the spatiotemporal dynamics of intracellular transport in cells undergoing LLPS are quantified. It is shown that intracellular diffusion and active transport are both reduced. Furthermore, the formation of SG droplets contributes to increased spatial heterogeneity within the cell. More importantly, the study demonstrated that the LLPS of SGs can be regulated by intracellular dynamics in two stages: the reduced intracellular diffusion promotes SG assembly and the microtubule‐associated transport facilitates SG coalescences. The work on intracellular dynamics not only improves the understanding of the mechanism of physiology phase separations occurring in nonequilibrium environments but also reveals an interplay between intracellular dynamics and LLPS. Live‐cell single‐particle tracking of quantum dots reveals the complex interplay between nonequilibrium dynamics and liquid–liquid phase separation (LLPS). Intracellular diffusion and active transport are reduced after LLPS, due to increased molecular crowding and heterogeneity of intracellular environments. Additionally, LLPS is regulated by intracellular dynamics: the reduced intracellular diffusion promotes stress granule (SG) assembly, and microtubule‐associated transport facilitates SG coalescence.