# Polyelectrolyte Nature of Cytoskeleton Filaments

> **NIH NIH SC1** · UNIVERSITY OF TEXAS SAN ANTONIO · 2021 · $375,000

## Abstract

Actin filaments (F-actin) and microtubules (MTs) are highly charged rod-like polyelectrolytes formed by
polymerization of G-actin and tubulin subunits, respectively. These cytoskeleton filaments are essential
for directional growth, shape, division and other important biological activities in eukaryotic cellular
processes. Mutations in G-actin / tubulin genes are often evident in pathological conditions. Actin
mutations may cause dilated or hypertrophic cardiomyopathies, congenital skeletal myopathies and
deafness. Whereas tubulin mutations are associated with fetal malformations of cortical development.
When subjected to intracellular biological environment alterations, even normal G-actin and tubulin
genes are associated with dysfunctions and malformations in F-actins / Mts such as dysregulated
assembly, misleading protein binding, abnormal polymerization stability, and defective electric signal
transmission. The basis for cytoskeleton filaments to transmit electric signals and overcome electrostatic
interactions to form bundles and networks appears primarily dominated by the polyelectrolyte nature of
these filaments rather than their tertiary structures. However, the underlying biophysical principles and
molecular mechanisms that support the polyelectrolyte nature of F-actin and MTs, and their properties
are still poorly understood due to the lack of appropriate methodologies. In this research project an
innovative approach for cytoskeleton filaments is proposed to balance accurate and efficient
computational tools with experimental techniques, making it possible for the first time, to
comprehensively and efficiently characterize bundling formation and electric signal propagation under the
numerous intracellular environments and filament molecular structures that are usually present in normal
and pathological conditions. It is hypothesized that molecular and/or cellular alterations, often evident in
pathological conditions caused by age and inheritance, break down equilibrium and competition between
the molecular mechanisms that dominate the bundling and conducting properties of cytoskeleton
filaments in normal conditions. The overall goal of this research proposal is to determine the impact of
excessive alterations in the intracellular environment and variations in the filament charge produced by
isoforms and mutations on the polyelectrolyte properties of cytoskeleton filaments. The outcomes of this
proposal is expected to provide an unprecedented molecular understanding on why and how age and
inheritance conditions induce dysfunctions and malformation in cytoskeleton filaments. This
understanding may advance the prevention and/or treatment of a variety of diseases. It may also open
unexplored frontiers in neuroscience. It might elucidate whether cytoskeleton filaments and axon
membranes are able to transmit different kind of information and what might be the role of electrical
signal propagation along filaments in neuronal cable-like theorie...

## Key facts

- **NIH application ID:** 10179425
- **Project number:** 5SC1GM127187-04
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Marcelo Marucho
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179425

## Citation

> US National Institutes of Health, RePORTER application 10179425, Polyelectrolyte Nature of Cytoskeleton Filaments (5SC1GM127187-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10179425. Licensed CC0.

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