# Biophysical Principles of Microtubule Dynamics

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2020 · $392,499

## Abstract

PROJECT SUMMARY
BIOPHYSICAL PRINCIPLES OF MICROTUBULE DYNAMICS
Microtubules are cytoskeletal polymers essential for cell division, cell motility and intracellular transport, and
are implicated in many cancers and neurological disorders. Remodeling of the microtubule network
architecture in space and time relies on the ability of individual microtubules to switch between periods of
growth and shrinkage, behavior known as `microtubule dynamic instability'. Although discovered more than
thirty years ago, the molecular mechanisms of microtubule dynamic instability and its regulation remain largely
unknown. This problem is exacerbated by a complex and highly interconnected network of microtubule-
associated proteins, which collectively regulate microtubule dynamics inside of cells. The goal of this project is
to provide a fundamental molecular understanding of microtubule behavior and its regulation. To accomplish
this goal, we will use an interdisciplinary approach, combining biology and physics. Inspired by conceptual
models developed using cell biological tools, we will employ biochemical in vitro reconstitution with purified
protein components, single-molecule total-internal-fluorescence (TIRF) imaging, and microfluidics techniques
to obtain a quantitative description of the microtubule system behavior. Microtubule length distributions are
determined by the combination of microtubule growth rates, shrinkage rates and the rates of transitions from
growth to shrinkage (catastrophe) and back (rescue). However, these four parameters are only a manifestation
of the underlying molecular mechanisms that define the macroscopic parameter values and their mutual
relationships. We will address the key question of the coupling between microtubule growth and catastrophe by
probing previously unattainable experimental regimes, critical for rigorous testing of existing and the
development of new theoretical models. We will perform detailed measurements of the microtubule minus end
dynamics, which to date remains largely unstudied, although recently recognized to be actively regulated
inside cells. We will determine the molecular mechanisms of microtubule rescue, least well understood
parameter of dynamic instability, which plays an important role in interphase microtubule architecture. Our
measurements will be performed with purified tubulin, as well as ensembles of microtubule-associated proteins
(including end-binding EB proteins, TOG-domain XMAP215 and CLASP proteins, and kinesin motor proteins
from Kinesin-13 and -14 families) in order to elucidate their collective effects on microtubule behavior. Based
on this quantitative characterization, we will develop predictive mathematical models that will capture the
fundamental principles of microtubule dynamics and its regulation. The predictions of our quantitative models
will be tested inside cells. This combination of theory and experiment will provide fundamental insight into
microtubule system regulation, ult...

## Key facts

- **NIH application ID:** 9995507
- **Project number:** 5R35GM119552-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Marija Zanic
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,499
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995507

## Citation

> US National Institutes of Health, RePORTER application 9995507, Biophysical Principles of Microtubule Dynamics (5R35GM119552-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995507. Licensed CC0.

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