Physical basis of large microtubule aster growth.

Keisuke Ishihara,Timothy J Mitchison,Kirill S Korolev

doi:10.7554/elife.19145

Keisuke Ishihara, Timothy J Mitchison + Show 1 more

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https://doi.org/10.7554/elife.19145

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Abstract

Microtubule asters - radial arrays of microtubules organized by centrosomes - play a fundamental role in the spatial coordination of animal cells. The standard model of aster growth assumes a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we recently found evidence for non-centrosomal microtubule nucleation. Here, we combine autocatalytic nucleation and polymerization dynamics to develop a biophysical model of aster growth. Our model predicts that asters expand as traveling waves and recapitulates all major aspects of aster growth. With increasing nucleation rate, the model predicts an explosive transition from stationary to growing asters with a discontinuous jump of the aster velocity to a nonzero value. Experiments in frog egg extract confirm the main theoretical predictions. Our results suggest that asters observed in large fish and amphibian eggs are a meshwork of short, unstable microtubules maintained by autocatalytic nucleation and provide a paradigm for the assembly of robust and evolvable polymer networks.

Highlights

Animal cells use asters, radial arrays of microtubules, to spatially organize their cytoplasm (Wilson, 1896)
By combining theory and experiments, we provide a quantitative framework for how the cell cycle may regulate the balance between polymerization dynamics and nucleation to control aster growth
Conceptual model for aster growth based on polymerization dynamics and autocatalytic nucleation

Summary

Introduction

Radial arrays of microtubules, to spatially organize their cytoplasm (Wilson, 1896). Individual microtubules undergo dynamic instability (Mitchison and Kirschner, 1984): They either grow (polymerize) or shrink (depolymerize) at their plus ends and stochastically transition between these two states. The collective behavior of microtubules is less well understood, and it is not clear how dynamic instability of individual microtubules controls aster growth and function. The standard model of aster growth posits that centrosomes nucleate and anchor all microtubules at their minus ends while the plus ends polymerize outward via dynamic instability (Brinkley, 1985). Aster growth is completely determined by the dynamics of individual microtubules averaged over the growing and shrinking phases. The aster either expands at a velocity given by the net growth rate of microtubules or remains stationary if microtubules are unstable and tend to depolymerize (Belmont et al, 1990; Dogterom and Leibler, 1993; Verde et al, 1992)

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