Modeling the effects of lattice defects on microtubule breaking and healing

Nan Jiang, Megan E. Bailey, Jessica Burke, Jennifer L. Ross, Ruxandra I. Dima

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Microtubule reorganization often results from the loss of polymer induced through breakage or active destruction by energy-using enzymes. Pre-existing defects in the microtubule lattice likely lower structural integrity and aid filament destruction. Using large-scale molecular simulations, we model diverse microtubule fragments under forces generated at specific positions to locally crush the filament. We show that lattices with 2% defects are crushed and severed by forces three times smaller than defect-free ones. We validate our results with direct comparisons of microtubule kinking angles during severing. We find a high statistical correlation between the angle distributions from experiments and simulations indicating that they sample the same population of structures. Our simulations also indicate that the mechanical environment of the filament affects breaking: local mechanical support inhibits healing after severing, especially in the case of filaments with defects. These results recall reports of microtubule healing after flow-induced bending and corroborate prior experimental studies that show severing is more likely at locations where microtubules crossover in networks. Our results shed new light on mechanisms underlying the ability of microtubules to be destroyed and healed in the cell, either by external forces or by severing enzymes wedging dimers apart.

Original languageEnglish (US)
Pages (from-to)3-17
Number of pages15
JournalCytoskeleton
Volume74
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • atomic force spectroscopy
  • coarse-grained simulations
  • katanin
  • microtubule mechanics
  • microtubule severing enzymes
  • spastin

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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