Holly V. Goodson | Searcharxiv

arXiv2013

Microtubule dynamic instability: the role of cracks between protofilaments

Microtubules (MTs) are cytoplasmic protein polymers that are essential for fundamental cellular processes including the maintenance of cell shape, organelle transport and formation of the mitotic spindle. Microtubule dynamic instability is critical for these processes, but it remains poorly understood, in part because the relationship between the structure of the MT tip and the growth/depolymerization transitions is enigmatic. What are the functionally significant aspects of a tip structure that is capable of promoting MT growth, and how do changes in these characteristics cause the transition to depolymerization (catastrophe)? Here we use computational models to investigate the connection between cracks (laterally unbonded regions) between protofilaments and dynamic instability. Our work indicates that it is not the depth of the cracks per se that governs MT dynamic instability. Instead it is whether the cracks terminate in GTP-rich or GDP-rich areas of the MT that governs whether a particular MT tip structure is likely to grow, shrink, or transition: the identity of the crack-terminating subunit pairs has a profound influence on the moment-by-moment behavior of the MT.

q-bio.BM↗

arXiv2006

Analysis of a microscopic stochastic model of microtubule dynamic instability

A novel theoretical model of dynamic instability of a system of linear (1D) microtubules (MTs) in a bounded domain is introduced for studying the role of a cell edge in vivo and analyzing the effect of competition for a limited amount of tubulin. The model differs from earlier models in that the evolution of MTs is based on the rates of single unit (e.g., a heterodimer per protofilament) transformations, in contrast to postulating effective rates/frequencies of larger-scale changes, extracted, e.g., from the length history plots of MTs. Spontaneous GTP hydrolysis with finite rate after polymerization is assumed, and theoretical estimates of an effective catastrophe frequency as well as other parameters characterizing MT length distributions and cap size are derived. We implement a simple cap model which does not include vectorial hydrolysis. We demonstrate that our theoretical predictions, such as steady state concentration of free tubulin, and parameters of MT length distributions, are in agreement with the numerical simulations. The present model establishes a quantitative link between microscopic parameters governing the dynamics of MTs and macroscopic characteristics of MTs in a closed system. Lastly, we use a computational Monte Carlo model to provide an explanation for non-exponential MT length distributions observed in experiments. In particular, we show that appearance of such non-exponential distributions in the experiments can occur because the true steady state has not been reached, and/or due to the presence of a cell edge.

q-bio.SC↗