Mathematical modeling of the microtubule detyrosination/tyrosination cycle for cell-based drug screening design.

ABSTRACT: Microtubules and their post-translational modifications are involved in major cellular processes. In severe diseases such as neurodegenerative disorders, tyrosinated tubulin and tyrosinated microtubules are in lower concentration. We present here a mechanistic mathematical model of the microtubule tyrosination cycle combining computational modeling and high-content image analyses to understand the key kinetic parameters governing the tyrosination status in different cellular models. That mathematical model is parameterized, firstly, for neuronal cells using kinetic values taken from the literature, and, secondly, for proliferative cells, by a change of two parameter values obtained, and shown minimal, by a continuous optimization procedure based on temporal logic constraints to formalize e

SUBMITTER: Grignard J 

PROVIDER: S-EPMC9236252 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature