# Mechanisms of cell shape change in cytokinesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $336,280

## Abstract

Amy Shaub Maddox
Project Summary
 Our bodies are intricate ensembles of trillions of cells, and these building blocks are not generic like the
bricks of a building, but rather are highly specialized. One characteristic of cells that distinguishes different types
is their shape, from spherical, as in your circulating immune cells, to highly elongated, exemplified by the neurons
that reach from our spines far into our legs. This project is aimed at understanding the mechanisms of cell shape
change, which is crucial for many cell functions, including when a cell pinches into two after duplicating its
contents.
 For 40 years, we have known that cell shape is maintained by some of the same cellular chemicals that
cause our muscles to contract: actin, which forms long flexible polymers, and myosin, a biological motor that
turns chemical energy into movement. Throughout these decades, substantial progress has been made in
understanding how cells build actin polymers and turn on myosin motors, but less is known about how these
essential events are attenuated. We reasoned that, just as the electronic governor on a heavy-duty truck limits
its velocity, cells have ways of limiting actin-myosin work, to tune cell shape.
 In this project, we present several pieces of preliminary evidence of such cellular governors. We propose
to determine the microscopic rearrangements that cause larger-scale cell shape changes, and define the
chemicals that control these rearrangements. First, we demonstrate that the actin-myosin meshwork ring that
pinches a cell in two does not go as fast as it can, but undergoes oscillations, speeding up and slowing down as
it constricts. We routinely use powerful microscopes to observe living cells as they pinch in half, and measure
the rearrangements that underlie these oscillations. Second, we will focus on the regulation of myosin, testing
three distinct ideas about how its activity could be limited. Last, we present three new directions for the old field
of studying cells pinching in half. To discover new candidate governors, we combined several technologies in
“fishing expedition” projects, which we have already completed. This unbiased but risky work laid well-
substantiated groundwork for our functional studies of these new candidates.
 In sum, this project will take our field of cell pinching into novel territory, and will be relevant to the study
of situations wherein cells purposefully arrest the pinching process, such as the generation of the specialized
cells in your liver and heart muscle. Our findings will also contribute general principles of cell change shape, and
thus help us understand normal development and diseases. Our discoveries may, in the long term, inform the
development of therapies for pathologies involving cell shape regulation, such as cancers and blood diseases.

## Key facts

- **NIH application ID:** 9995487
- **Project number:** 5R01GM102390-10
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Amy Shaub Maddox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,280
- **Award type:** 5
- **Project period:** 2012-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995487

## Citation

> US National Institutes of Health, RePORTER application 9995487, Mechanisms of cell shape change in cytokinesis (5R01GM102390-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995487. Licensed CC0.

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