# Physics of bronchial epithelial unjamming

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $557,405

## Abstract

Abstract
A confluent collective of epithelial cells lines every organ surface and body cavity. The epithelial collective
typically remains quiescent and non-migratory while performing its routine barrier and immune functions, but
becomes dynamic and migratory during embryonic development and airway morphogenesis, during airway
repair and asthmatic airway remodeling, as well as during carcinoma invasion and metastasis. In these and
other processes, the striking transition between non-migratory versus migratory behaviors is traditionally
framed within the context of the epithelial-to-mesenchymal transition (EMT) or the partial EMT (pEMT). During
pEMT the epithelial phenotype, which is said to be innately non-migratory, transitions toward a mesenchymal
phenotype, which is innately migratory. But to initiate and sustain collective cellular migration, our central
hypothesis holds that the EMT/pEMT mechanism as it is canonically defined is not obligatory. Rather, we
propose that the newly discovered unjamming transition (UJT) mechanism in many cases elicits collective
cellular migration and, importantly, can function independently of the EMT or pEMT. Unjamming is not to be
mistaken for cellular migration or for remodeling. But unjamming does create the physical conditions that make
cellular migration and remodeling possible. Using the confluent layer of primary human bronchial epithelial
cells (HBECs) in air-liquid-interface (ALI) culture, here we propose to: 1) establish the UJT mechanism as an
independent route to collective HBEC migration; 2) map in HBECs the molecular interactome of the UJT
mechanism; and 3) explain molecular, structural, and migratory features that typify the UJT mechanism.
Extensive preliminary data support the tenability of these aims, which are designed to illuminate basic
mechanisms that differentiate UJT from EMT.

## Key facts

- **NIH application ID:** 9995569
- **Project number:** 5R01HL148152-02
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Jeffrey J Fredberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $557,405
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995569

## Citation

> US National Institutes of Health, RePORTER application 9995569, Physics of bronchial epithelial unjamming (5R01HL148152-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995569. Licensed CC0.

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