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Mechanical coupling coordinates microtubule growth.

Bonnibelle K Leeds1, Katelyn F Kostello1, Yuna Y Liu1

  • 1Department of Physiology & Biophysics, University of Washington, Seattle, United States.

Elife
|December 27, 2023
PubMed
Summary
This summary is machine-generated.

Mechanical forces synchronize microtubule growth during cell division. This study reveals how force-dependent pausing and varied growth speeds coordinate microtubule bundles (k-fibers) for accurate chromosome segregation.

Keywords:
B. taurusS. cerevisiaecell biologycoordinationdynamic instabilityhumank-fiberkinetochoremechanobiologymicrotubulemitosisphysics of living systemsspindlestochastic pausing

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Area of Science:

  • Cell Biology
  • Biophysics

Background:

  • During mitosis, kinetochore-microtubule fibers (k-fibers) exhibit coordinated growth and shortening for chromosome alignment and segregation.
  • Individual microtubule dynamics are intrinsically variable, necessitating tight regulation for k-fiber unity.
  • Coordination mechanisms may be biochemical (polymerase/depolymerase activity) or mechanical (shared load).

Purpose of the Study:

  • To investigate the role of mechanical coupling in synchronizing microtubule growth within k-fibers.
  • To elucidate the mechanisms underlying the coordinated behavior of microtubule bundles during mitosis.

Main Methods:

  • Utilized a novel dual laser trap assay to study pairs of microtubules growing in vitro.
  • Performed kinetic analyses to characterize microtubule growth dynamics, including pauses and speed variations.
  • Developed a computational model incorporating force-dependent pausing and growth speed heterogeneity.

Main Results:

  • Demonstrated that mechanical coupling coordinates the growth of paired microtubules in vitro.
  • Identified stochastic, force-dependent pauses as a key feature of microtubule growth.
  • Observed persistent heterogeneity in microtubule growth speeds during non-pausing periods.
  • A model combining force-dependent pausing and growth heterogeneity accurately predicted microtubule pair coordination.

Conclusions:

  • Mechanical coupling, through force-dependent pausing and inherent growth speed variability, synchronizes microtubule growth in k-fibers.
  • Findings provide a mechanistic basis for understanding k-fiber coordination and chromosome segregation.
  • The study offers a foundation for modeling larger microtubule bundles found in eukaryotes.