# Mechanochemical regulation of actin-mediated cell protrusion

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $324,000

## Abstract

ABSTRACT
Cell migration can be divided into three mechanical processes: i) protrusion; ii) adhesion and
deadhesion; and iii) cytoskeleton contraction. These processes are coordinated by spatially and
temporally organized regulatory signals, many of which are mechano-responsive, i.e. the
signaling events are modulated by the mechanical forces they regulate. As the first of the three
processes protrusion defines the directionality and persistence of cell movements. The
protrusion machinery is also the integrator of internal and external guidance cues, including
polarity, chemotactic, haptotactic, and durotactic stimuli. Accordingly, cell protrusion in itself is
the result of complex intersections between mechanical and chemical signaling pathways that
translate the various inputs into the coordinated activation of pathways that push the cell edge
forward. While it is safe to assume that the molecular constituents of these pathways are largely
known, we have very little understanding of the mechanism of pathway integration. Here we
focus on actin-based protrusion. Dissecting the system of pathways that regulate actin-based
protrusions remains a formidable challenge because of the substantial functional overlap and
non-linear (feedback and feed forward) relations between pathways. Conventional perturbation
approaches, which disrupt one pathway at a time, yield largely uninterpretable results because
the overall pathway system immediately adapts. The overarching theme of this proposal is
therefore the development of an analytical framework that relies on measuring basal fluctuations
of pathway activities in molecularly unperturbed and spontaneous cell protrusions and on
statistical inference of the functional hierarchy and timing among intersecting pathways using
stochastic time series analysis. The proposed analytical framework will provide unprecedented
data on the topology and kinetics of information flows in non-linear and partially redundant
pathway systems. While cell protrusion is a particularly attractive problem to develop and
demonstrate the power of basal fluctuation analysis the analytical tools to be developed will be
general and thus applicable to other cell biological investigations. Building on our findings of the
previous funding period we will apply the analytical framework to test hypotheses on the
coordination of pathways that initiate and upregulate actin filament assembly in persistent
protrusion events during directed migration.

## Key facts

- **NIH application ID:** 9847967
- **Project number:** 5R01GM071868-10
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Gaudenz Danuser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,000
- **Award type:** 5
- **Project period:** 2007-04-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847967

## Citation

> US National Institutes of Health, RePORTER application 9847967, Mechanochemical regulation of actin-mediated cell protrusion (5R01GM071868-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9847967. Licensed CC0.

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