Anomalous Coarsening of Coalescing Nucleoli in Human Cells

Biophys J. 2024 Jan 8:S0006-3495(24)00006-7. doi: 10.1016/j.bpj.2024.01.005. Online ahead of print.ABSTRACTCoarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium - as an increase in droplet size lowers the system's free energy - however, coarsening of droplets in non-equilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coalescing with each other. Upon coarsening, human nucleoli exhibit an anomalous volume distribution P(V) ∼ V-1, which cannot be explained by any existing theory. In this work, we investigate physical mechanisms behind the anomalous coarsening of human nucleoli. Using spinning disc confocal microscopy, we simultaneously record dynamical behavior of nucleoli and their surrounding chromatin prior to their coalescence in live human cells. We find that nucleolar anomalous coarsening persists during the entire cell cycle. We measure chromatin flows and density between and around nucleoli, as well as relative motion of two nucleoli before they coalesce. We find that prior to nucleolar coalescence chromatin concentration decreases in the space between nucleoli and the nucleoli move faster towards each other, resembling an effective depletion attraction between the coal...

Source: Biophysical Journal - January 9, 2024 Category: Physics Authors: Giorgi Arsenadze Christina M Caragine Taylor Coakley Iraj Eshghi Yuwei Yang Alex Wofford Alexandra Zidovska Source Type: research