# Modeling mechanisms in cytokinesis, cell polarization and motility

> **NIH NIH R35** · LEHIGH UNIVERSITY · 2021 · $427,683

## Abstract

Project Summary/Abstract
The ability of cells to divide, establish a polarization direction, and move by crawling requires the coordinated
interactions of the cytoskeleton with membranes as well as with the signaling system organizing on
membranes. A major challenge for the development of predictive mathematical and computational models of
these mechanisms of subcellular organization is accounting of how highly specific interactions at the molecular
level lead to the emergent collective behavior. We propose to address this complexity by employing powerful
computational and modeling methods linking molecular to cellular scales, in close collaboration with
experimentalists working on model systems that (i) reveal important cell biological functions and (ii) are
amenable to quantitative approaches. The proposed research program will address mechanisms in
cytokinesis, cell polarization and motility. A. Cytokinesis. We have previously modeled how the contractile ring
in fission yeast forms through the condensation a broad band of membrane-bound nodes containing myosin
and formin. These models represented nodes, which are large macromolecular complexes, as single units with
the ability to polymerize and pull actin. Using input from super-resolution experiments and applying coarse-
grained biophysical modeling and Bayesian inference methods, we propose to model the ultrastructure and
dynamics of nodes, how this organization impacts their ability to capture and pull actin filaments, as well as the
role of type V myosin. We will develop models to study how membrane delivery is distributed across the whole
septum and how it coordinates with contractile ring constriction and tension. B. Cell polarization and ER
organization. We will study how the Cdc42/Ras1 system establishes patterns with distinct spatial distributions
of GEF and GAP regulators on cell membrane. Novel modeling methods will be developed to understand how
the ER membrane is distributed subcellularly on cortical sheets adhered to the plasma membrane, cortical
fenestrae anchored to eisosomes and internal tubular networks, altogether regulating cell polarization. C. Actin
dynamics in motile cells. We will develop filament-level models of actin dynamics and organization in
lamellipodia that account for their dendritic network structure, distributed turnover, force transmission and
mechanical regulation of branching, severing and polymerization. In collaboration with the Watanabe group
(Kyoto University), we will test these models by measuring turnover and flows near focal adhesions with single
molecule imaging of actin and regulators.

## Key facts

- **NIH application ID:** 10134377
- **Project number:** 5R35GM136372-02
- **Recipient organization:** LEHIGH UNIVERSITY
- **Principal Investigator:** Dimitrios Vavylonis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $427,683
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134377

## Citation

> US National Institutes of Health, RePORTER application 10134377, Modeling mechanisms in cytokinesis, cell polarization and motility (5R35GM136372-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134377. Licensed CC0.

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