# Functional Roles of the Membrane Phase Transition in Cellular Physiology

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $628,538

## Abstract

PROJECT SUMMARY
The plasma membrane dictates how cells sense and respond to their environment, informing
cellular decisions to, for example, proliferate, mature into other cell types, respond to
pathogens, transmit electrical signals, or strengthen neuronal connections in the brain. Lipids
and proteins within membranes act collectively to provide both a physical barrier to the
extracellular space and the ability to selectively transmit information and materials to the cell.
Defects in these processes lead to diverse human diseases ranging from cancer to
immunodeficiency to neurodegeneration. Work in the PI’s lab seeks to discover how collective
behaviors of membranes contribute to cellular sensing, combining physically rigorous
thermodynamic models with single-molecule, supper-resolution fluorescence imaging and
functional studies of signaling outcomes. The plasma membrane undergoes a liquid-liquid
phase transition, and recent work from the PIs lab demonstrates that this phase transition
enables membranes to adapt their compositions locally in response to external stimuli,
establishing a heterogeneous environment that can impact membrane biochemistry to induce or
modulate a functional response. Future work will explore the ways in which this highly
susceptible membrane state shapes the functional outcomes of cell sensing, focusing on
signaling systems relevant to immune recognition and on the functioning of individual ion
channel receptors found at inhibitory synapses within neurons. Work in immune cells will
explore the roles of membranes in regulating the biochemical networks responsible for sensing
in these cell types, exploring the impact of receptor clustering, lipid homeostasis, and protein
scaffolds such as cortical actin and condensed platforms of adaptor proteins that often
assemble at membranes as part of signaling cascades. Work with ion channels will probe
impacts of the membrane phase transition on the functioning of single proteins, exploring
theoretical predictions of allosteric regulation by membranes and the chemical availability of
hydrophobic effectors of channel activation. Future research will also begin to probe internal
membranes, such the nuclear envelope, extending methods established in the PI’s lab to
determine if and/or how these membranes exploit consequences of the phase transition.
Through discovery of underlying mechanisms, the overall vision of the research program is to
identify new approaches to influence cell sensing through manipulations of membrane
properties, informing new strategies for the treatment of human disease.

## Key facts

- **NIH application ID:** 10767491
- **Project number:** 1R35GM152150-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sarah L Veatch
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $628,538
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767491

## Citation

> US National Institutes of Health, RePORTER application 10767491, Functional Roles of the Membrane Phase Transition in Cellular Physiology (1R35GM152150-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10767491. Licensed CC0.

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