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

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $446,090

## Abstract

PROJECT SUMMARY:
Vimentin intermediate filaments augment cytoskeletal deformability and directed migration of
individual mesenchymal cells, but their role in multicellular migration, tractions, and coordination is
poorly understood. Such collective migration of mechanically connected cells is crucial for embryonic
development, wound healing, and tumor invasion. Gain of vimentin is associated with the epithelial-
mesenchymal transition (EMT), where tightly-connected epithelial cells downregulate cell-cell adhesions and
acquire an individual mesenchymal phenotype. However, cells that migrate collectively in groups can also
express vimentin in combination with cell-cell junctions (e.g. cadherins). For instance, “leader cells” at wound
fronts can exhibit an elongated morphology with vimentin, while remaining partially connected to migratory
followers. Given these questions, there exists a critical need to elucidate the role of vimentin in leader cells
and its contributions to collective cell migration.
 Our overall objective is to elucidate the functional role of vimentin in leader and follower cells for directed
cell motility, multicellular tractions, and cell-cell coordination. In particular, we consider several fundamental
questions: 1) How does vimentin affect confined migration and cellular deformability? 2) How does vimentin
affect collective tractions? 3) How does vimentin affect cell-cell adhesions and coordinated motility? 4) How do
vimentin-high and vimentin-low cells interact during collective migration?
 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 an
Early Stage 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 in collective
migration, with potential implications for tissue morphogenesis and tumor dissemination.

## Key facts

- **NIH application ID:** 10099773
- **Project number:** 1R01GM140108-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ming Guo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $446,090
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10099773

## Citation

> US National Institutes of Health, RePORTER application 10099773, Mechanobiology of Vimentin Intermediate Filaments in 3D Collective Cell Migration (1R01GM140108-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10099773. Licensed CC0.

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