The mechanisms of microtubule catastrophe and rescue: implications from analysis of a dimer-scale computational model

Margolin, Gennady; Gregoretti, Ivan V.; Cickovski, Trevor; Li, Chunlei; Shi, Wei; Alber, Mark; Goodson, Holly V.

doi:10.1091/mbc.e11-08-0688

Cited by 113 publications

(195 citation statements)

References 65 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…As recently discussed by Margolin et al [15], the results from all models, by parameter tuning, appear to agree with available experimental observations irrespective of the details of microtubule structure included, and irrespective of the differences in mathematical expressions for (primarily) the frequency of catastrophe or related quantities. We feel that a comparative study of at least some of the models, from a common starting point, is desirable, and this is one of the objectives of this paper.…”

Section: Introductionsupporting

confidence: 78%

“…Our approach in this paper is essentially kinetic in nature, and we do not propose to undertake a detailed treatment of the energetics in the problem, which has been carried out by several authors [11][12][13]15]. For this reason, we do not consider explicitly the energy of interaction between protofilaments or the bending energy of individual protofilaments.…”

Section: Model and Definitionsmentioning

confidence: 99%

“…Therefore, we may use the av ailable estimates of k d as a measure of k h . Margolin et al [15] estimated that k d ∼ 1 − 10s −1 , by studying the experimental data of Gardner et al [26], depending on the tubulin concentration. It turned out that a high k h value is necessary to reproduce the experimental data of [26], and therefore, we fixed k h =7s −1 and tuned r, for each n * , such that the steady state value of microtubule catastrophe is comparable to the experimental value 0.005s −1 for k g = 24.375s −1 (corresponding to a growth velocity v g = 15nms −1 in the experiment, with the simple conversion formula k g = v g /δ with δ = 8nm/13 = 0.6nm).…”

Section: B Numerical Simulationsmentioning

confidence: 99%

“…A large variety of approaches have been adopted to tackle the problem of microtubule dynamics based on the GTP cap theory [6][7][8][9][10][11][12][13][14][15], which differ essentially in the level of molecular details included in the respective models. As recently discussed by Margolin et al [15], the results from all models, by parameter tuning, appear to agree with available experimental observations irrespective of the details of microtubule structure included, and irrespective of the differences in mathematical expressions for (primarily) the frequency of catastrophe or related quantities.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Microtubule catastrophe from protofilament dynamics

Jemseena¹,

Gopalakrishnan²

2013

Phys. Rev. E

View full text Add to dashboard Cite

The disappearance of the guanosine triphosphate (GTP)-tubulin cap is widely believed to be the forerunner event for the growth-shrinkage transition ('catastrophe') in microtubule filaments in eukaryotic cells. We study a discrete version of a stochastic model of the GTP cap dynamics, originally proposed by Flyvbjerg, Holy andLeibler (Flyvbjerg, Holy and Leibler, Phys. Rev. Lett. 73, 2372, 1994). Our model includes both spontaneous and vectorial hydrolysis, as well as dissociation of a non-hydrolyzed dimer from the filament after incorporation. In the first part of the paper, we apply this model to a single protofilament of a microtubule. A catastrophe transition is defined for each protofilament, similar to the earlier one-dimensional models, the frequency of occurrence of which is then calculated under various conditions, but without explicit assumption of steady state conditions. Using a perturbative approach, we show that the leading asymptotic behavior of the prot ofilament catastrophe in the limit of large growth velocities is remarkably similar across different models. In the second part of the paper, we extend our analysis to the entire filament by making a conjecture that a minimum number of such transitions are required to occur for the onset of microtubule catastrophe. The frequency of microtubule catastrophe is then determined using numerical simulations, and compared with analytical/semi-analytical estimates made under steady state/quasi-steady state assumptions respectively for the protofilament dynamics. A few relevant experimental results are analyzed in detail, and compared with predictions from the model. Our results indicate that loss of GTP cap in 2-3 protofilaments is necessary to trigger catastrophe in a microtubule.

show abstract

Section: Introductionsupporting

confidence: 78%

Section: Model and Definitionsmentioning

confidence: 99%

Section: B Numerical Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Microtubule catastrophe from protofilament dynamics

Jemseena¹,

Gopalakrishnan²

2013

Phys. Rev. E

View full text Add to dashboard Cite

show abstract

“…For a more comprehensive model, finer detail on the structure of the cap, potentially influenced by the nanoscale structure of the microtubule end itself, such as the tapered or sheet-like extensions observed by electron microscopy (48) may have to be considered (51). Furthermore, defects (45) or lattice cracks (52)(53)(54) have been hypothesized to exist and to provide alternative or additional constraints on microtubule stability (45,50,53,54). Unfortunately, unlike cap size fluctuations, the real-time observation of these other features is currently not possible, limiting direct tests of these models.…”

Section: Discussionmentioning

confidence: 99%

Steady-state EB cap size fluctuations are determined by stochastic microtubule growth and maturation

Rickman

Duellberg

Cade

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steadystate growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.microtubules | dynamic instability | GTP cap | EB1 | biochemical network

show abstract

Chemically Fueled Self‐Assembly in Biology and Chemistry

2021

View full text Add to dashboard Cite

moved to Italy to join the group of Leonard Prins at the University of Padova as aMarie Curie Seal-of-Excellence@UNIPD fellow to work on the dissipative self-assemblyo f chemical nanoreactors. His research interests include systems chemistry and non-equilibrium supramolecular systems. Luca Gabrielli received his PhD from the University of Milano-Bicocca (2013), under the supervision of Prof L. Cipolla. After postdoctoral research in the groups of Prof.

show abstract

The mechanisms of microtubule catastrophe and rescue: implications from analysis of a dimer-scale computational model

Cited by 113 publications

References 65 publications

Microtubule catastrophe from protofilament dynamics

Microtubule catastrophe from protofilament dynamics

Steady-state EB cap size fluctuations are determined by stochastic microtubule growth and maturation

Chemically Fueled Self‐Assembly in Biology and Chemistry

Contact Info

Product

Resources

About