TY - JOUR
T1 - A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches
AU - Setru, Sagar U.
AU - Gouveia, Bernardo
AU - Alfaro-Aco, Raymundo
AU - Shaevitz, Joshua W.
AU - Stone, Howard A.
AU - Petry, Sabine
N1 - Funding Information:
We thank S. Lee, T.-M. Chou and M. Libera at Stevens Institute of Technology for access to their atomic force microscope; I. Armstrong and S. Dutta at Bruker for access to and support for their atomic force microscope; M. King, B. Bratton, M. Safari, M. Koch, P. Ronceray and N. Wingreen for discussions; A. Thawani for purification of TPX2; H. Ando, C. Holmes, physiology students V. Baena, D. Laundon and L. Ma, and the Physiology Course at the Marine Biological Lab for assisting with the first AFM trials; and Princeton’s Imaging and Analysis Center, which is partially supported by the Princeton Center for Complex Materials, an NSF-MRSEC programme (DMR-1420541). B.G. was supported by PD Soros and NSF GRFP. S.U.S. was supported by NIH NCI NRSA 1F31CA236160 and NHGRI training grant 5T32HG003284. This work was funded by NIH NIA 1DP2GM123493, Pew Scholars Program 00027340, Packard Foundation 2014-40376 and CPBF NSF PHY-1734030.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/4
Y1 - 2021/4
N2 - Liquid–liquid phase separation1,2 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 nucleation3–5, which is critical for spindle assembly in eukaryotic cells6–10. 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 web11,12. 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.
AB - Liquid–liquid phase separation1,2 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 nucleation3–5, which is critical for spindle assembly in eukaryotic cells6–10. 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 web11,12. 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.
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U2 - 10.1038/s41567-020-01141-8
DO - 10.1038/s41567-020-01141-8
M3 - Article
C2 - 35211183
AN - SCOPUS:85099924136
SN - 1745-2473
VL - 17
SP - 493
EP - 498
JO - Nature Physics
JF - Nature Physics
IS - 4
ER -