A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches

Liquid-liquid phase separation(1,2) occurs not only in bulk liquid, but also on surfaces. In physiology, the nature and function of condensates on cellular structures remain unexplored. Here we study how the condensed protein TPX2 behaves on microtubules to initiate branching microtubule nucleation(3-5), which is critical for spindle assembly in eukaryotic cells(6-10). Using fluorescence, electron and atomic force microscopies and hydrodynamic theory, we show that TPX2 on a microtubule reorganizes according to the Rayleigh-Plateau instability, like dew droplets patterning a spider web(11,12). After uniformly coating microtubules, TPX2 forms regularly spaced droplets, from which branches nucleate. Droplet spacing increases with greater TPX2 concentration. A stochastic model shows that droplets make branching nucleation more efficient by confining the space along the microtubule where multiple necessary factors colocalize to nucleate a branch.

Automated summary

Liquid-liquid phase separation not only occurs in bulk liquid, but also on surfaces. In this study, it was found that the protein TPX2 on microtubules reorganizes according to the Rayleigh-Plateau instability to initiate branching microtubule nucleation. The spacing of droplets formed by TPX2 increases with higher TPX2 concentration, making branching nucleation more efficient by confining necessary factors in a smaller space along the microtubule.