# Membrane tension as a long-range integrator of cell physiology

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $119,339

## Abstract

PROJECT SUMMARY
Membrane tension is thought to be a long-range integrator of cell physiology. During migration, membrane
tension has been proposed to enable cell polarity through front-back coordination and long-range protrusion
competition. These roles necessitate effective tension transmission across the cell. However, it remains a
source of significant debate as to whether cell membranes support or resist long-range membrane tension
propagation. I speculated that this this discrepancy likely originates from the use of exogenous forces that
may not accurately mimic endogenous forces. To overcome this complication, I used optogenetics to directly
control localized actin-based protrusions or actomyosin contractions while simultaneously monitoring the
propagation of membrane tension using dual-trap optical tweezers. My results led me to propose a unifying
model of tension propagation in which actin-driven protrusions and actomyosin contractions both elicit rapid
global membrane tension propagation, while forces applied to cell membranes alone do not. This work laid
the foundations of my ongoing studies and raises many important questions. For some processes, membrane
tension needs to act locally and in others, it needs to act at the range of the entire cell or multiple cells. What
controls the range and efficiency of tension propagation (Aim 1)? The cell has many processes that can
locally initiate changes in membrane tension (protrusions, contractions) and many cellular processes that are
regulated by tension changes. Are there important functional differences for how these cellular programs
transmit or receive membrane tension changes that may be important for cell polarity (Aim 2)? Migrating cells
often need to coordinate their movement with other cells in order to achieve collective or cooperative motion.
What is the impact of the membrane tension-polarity program in multicellular contexts such as encountered
during collective or cooperative cell migration (Aim 3)? I will answer these questions by using a combination
of optogenetics, force measurements, and advanced microscopy, and mathematical modeling. My research
will elucidate the interplay between membrane mechanics and polarity during cell migration and will provide
the foundation for my independent scientific niche of studying membrane mechanics during transendothelial
migration. Towards this goal, I am supplementing the input of my postdoc supervisor, Dr Weiner (expert on
cell polarity during migration) with a group of internationally recognized leaders at the interface of cell biology
and biophysics: Carlos Bustamante (optical traps), Herve Turlier (mechanical modelling), Janis Burkhardt
(cell migration). Japp van Buul and Ronen Alon, both experts on transendothelial migration. These scientists
will act as both advisors and collaborators, helping me establish my own scientific niche in understanding the
role of membrane mechanics in regulating transendothelial migration. I have worked...

## Key facts

- **NIH application ID:** 10865382
- **Project number:** 1K99GM154115-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Henry De Belly
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $119,339
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865382

## Citation

> US National Institutes of Health, RePORTER application 10865382, Membrane tension as a long-range integrator of cell physiology (1K99GM154115-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10865382. Licensed CC0.

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