# Investigating the molecular regulation of cell protrusion function in 3D

> **NIH NIH R35** · UNIVERSITY OF MINNESOTA · 2024 · $300,477

## Abstract

PROJECT SUMMARY
Cells shape and reshape themselves as they accomplish diverse functions in vivo. These cell shape changes
result from physical and chemical feedback loops at multiple scales. At the biochemical scale, spatiotemporally
varying signaling cascades control cytoskeletal polymerization that pushes on the plasma membrane from the
inside, inducing cell morphology change at the scale of micrometers. Cell morphology in turn feedbacks to alter
intracellular signaling, via mechanisms such as surface curvature-sensing proteins in the plasma membrane.
Understanding these feedbacks across scales is particularly critical since they are a target for pharmaceutical
intervention. Scientists have developed a wealth of techniques for interrogating the biochemical and genetic
basis of cell function. However, disentangling the many feedback loops coupling cell morphology, intracellular
organization, and spatiotemporally varying biochemical pathways, such as intracellular signaling, remains ex-
perimentally challenging. Live-cell fluorescence microscopy can visualize these feedbacks in action, but imaging
across scales produces enormous and detailed datasets that are impossible to make sense of without dedicated
computational pipelines. We will develop algorithms for cell biology rooted in computational geometry. Using
computational geometry approaches will allow us to draw from decades of math and computer science research
to work in biologically relevant geometries, increasing accuracy and easing interpretation. We propose to develop
essential algorithms to reconstruct plasma membrane organization from 3D microscopy images and track its
movements across time. We will also measure the organizational rules that couple plasma membrane shape
and dynamics to spatiotemporally varying biochemical pathways on the cell surface. Finally, we will focus on
understanding feedbacks related to intracellular organization throughout the cell, not just on the plasma mem-
brane, by broadening the computational approaches we developed for the plasma membrane to other geome-
tries. The computational methods that we are proposing to develop will aid in further opening up to scientific
investigation the many feedback loops and physical interactions of the meso-scale world of subcellular organi-
zation.

## Key facts

- **NIH application ID:** 10938440
- **Project number:** 1R35GM155310-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Meghan Katrien Driscoll
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,477
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938440

## Citation

> US National Institutes of Health, RePORTER application 10938440, Investigating the molecular regulation of cell protrusion function in 3D (1R35GM155310-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10938440. Licensed CC0.

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