# Molecular basis of force-sensing by the keratin network

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $392,996

## Abstract

Project Summary
Physical integrity of epithelial tissue is established and maintained by the cytoskeletal network which integrates
cells into their environment with other neighboring cells and the extracellular matrix. In particular, keratin
intermediate filament proteins ubiquitously expressed in epithelial cells are responsible for the structural
integrity of epithelial tissues and recently emerged as a driver of collective cell migration. Yet, unlike actin,
understanding of keratin force-sensing is still very limited. We discovered that the keratin network responds to
externally applied physical forces by recruiting cten, a protein known to act as both a tumor suppressor and
promoter in a tissue-specific manner. Emerging evidence indicates that more proteins are recruited to the
force-bearing keratin fibers, suggesting that the keratin network may serve as a critical hub for
mechano-transduction. The overall premise of this application is that discovering the basic mechanisms and
functions of keratin-based mechano-sensing will contribute to the understanding of how the cell senses forces.
Our goal is to determine the force-dependent protein interactome surrounding the keratin network in epithelial
cells and how keratin-mediated mechano-transduction impacts cell behavior. To resolve force-sensitive
protein-protein interactions, we will inscribe proximal proteins by in situ promiscuous biotin labeling while cells
are being physically stimulated. Newly identified candidates will be tested to verify their force-dependent co-
localization with keratin filaments in live cells and in vitro, and analyzed for their roles in transcriptional
regulation, cell integrity maintenance, and collective cell migration. Our approach will reveal the comprehensive
list of keratin-associated proteins in the presence or absence of external forces and, for the first time, resolve
the force-dependent regulation of the keratin network and its physiological implications.

## Key facts

- **NIH application ID:** 10757455
- **Project number:** 5R01GM148706-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Soichiro Yamada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,996
- **Award type:** 5
- **Project period:** 2023-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757455

## Citation

> US National Institutes of Health, RePORTER application 10757455, Molecular basis of force-sensing by the keratin network (5R01GM148706-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10757455. Licensed CC0.

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