# Mechanobiology of Vimentin Intermediate Filaments in 3D Collective Cell Migration

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $147,703

## Abstract

PROJECT SUMMARY:
Vimentin intermediate filaments in the cytoskeleton play an underappreciated physiological role in
epithelial tissue development, repair, and tumor progression. In particular, vimentin knockout impairs
mouse mammary gland development and regeneration in vivo, and disrupts 2D collective cell migration in vitro.
Gain of vimentin is also associated with the epithelial-mesenchymal transition (EMT), where tightly-connected
epithelial cells downregulate cell-cell adhesions and increase motility. For instance, “leader cells” at wound
fronts can exhibit an elongated morphology with vimentin, while remaining partially connected to migratory
followers. Indeed, a combination of vimentin and keratin 14 are associated with partial EMT states in
genetically engineered mouse models of cancer. Nevertheless, the functional role of vimentin in multicellular
migration, tractions, and coordination remains poorly understood, particularly in 3D matrix.
 Our long-term goal is to elucidate how the mechanobiology of the cytoskeleton regulates collective
migration in organ formation, tissue repair, and disease. This goal requires addressing several fundamental
questions: 1) How does vimentin affect directed migration and cellular deformability? 2) How does vimentin
affect collective tractions? 3) How does vimentin affect cell-cell adhesions and collective migration? 4) How do
vimentin-high and vimentin-low cells interact during collective migration? Based on these challenges, our
objective is to elucidate the role of vimentin in collective migration through directed cell motility, multicellular
tractions, as well as cell-cell coordination.
 Our approach will integrate several complementary technologies for precision measurement of collective
cell migration and mechanobiology. MPI: Guo is an Early Stage Investigator with extensive expertise in the
mechanics of soft and living materials, including vimentin networks and extracellular matrix. MPI: Wong is a
New Investigator with extensive expertise in collective migration and EMT, particularly single cell tracking and
analyses. Co-I: Goldman is a leader in the molecular biology of vimentin. This proposal is structured around 3
aims: elucidate how vimentin affects cell shape, migration and deformability of multicellular collectives in
confinement (AIM 1), multicellular tractions in 3D matrix (AIM 2), and collective interactions of “mosaic”
spheroids with heterogeneous vimentin expression (AIM 3). Overall, this work will reveal new fundamental
insights into the role of vimentin in cell shape, motility, and mechanical integrity.

## Key facts

- **NIH application ID:** 11099158
- **Project number:** 3R01GM140108-04S1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ming Guo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $147,703
- **Award type:** 3
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099158

## Citation

> US National Institutes of Health, RePORTER application 11099158, Mechanobiology of Vimentin Intermediate Filaments in 3D Collective Cell Migration (3R01GM140108-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11099158. Licensed CC0.

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