Surface Fluctuations and Coalescence of Nucleolar Droplets in the Human Cell Nucleus

Abstract

The nucleolus is a membraneless organelle embedded in chromatin solution inside the cell nucleus. It is a site of ribosomal biogenesis, plays a key role in cell cycle progression and stress response, and acts as an indicator in many human diseases and aging. However, the physical nature of the human nucleolus remains an open question. Elucidating nucleolar dynamics, such as their shape fluctuations and fusion, could not only help answer this question, but also provide insight into the material properties of the surrounding nucleoplasm. In this work, we analyze the surface dynamics and fusion kinetics of nucleoli in live human cells[1]. Nucleolar surface fluctuations inform on the nucleolus-nucleoplasm interface, while nucleolar fusion might resolve whether nucleoli aggregate like solid particles or coalesce like liquid droplets. We find that the surface exhibits subtle, but measurable, fluctuations and that the neck connecting two fusing nucleoli grows as r(t)∼t1/2. This is consistent with liquid droplets with low surface tension ∼10−6 Nm−1 coalescing in an outer fluid of higher viscosity ∼103 Pa s, i.e. chromatin solution. We hypothesize that the high viscosity of chromatin solution slows down the nucleolar coalescence kinetics to facilitate transcription inside nucleoli. Interestingly, we find the neck velocity, dr/dt, to be comparable to the velocity of chromatin solution[2]. Surprisingly, nucleolar coalescence occurs in an active fluid, yet can be described by coalescence theory for passive liquid droplets, suggesting that the measured viscosity and surface tension might be effective quantities. Our study presents a noninvasive approach of using natural probes, such as nucleoli, and their dynamics to investigate material properties of the cell and its constituents[1]. 1. Caragine CM et al., Phys. Rev. Lett., In Press, 2018. 2. Zidovska A et al., Proc. Natl. Acad. Sci., 110(39), 15555-60, 2013.