# The cross-scale biomechanics of tissue morphogenesis

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $410,375

## Abstract

Dynamic molecular interactions among cell adhesion proteins, the extracellular matrix
(ECM) and the cytoskeleton give rise to tissue-level mechanics, but delineating the
mechanism of emergence of spatiotemporally regulated tissue mechanics remains a
challenge. This proposal addresses this problem utilizing an integrated cross-scale
approach that quantifies molecular scale protein movement and protein-protein association
as well as tissue mechanics using cell tracking and quantitative metrics from fluid
mechanics. Specifically, the assembly of the paraxial mesoderm from motile mesodermal
progenitors is examined. The proposal seeks to elucidate a regulatory mechanism in which
Fibronectin fibrillogenesis is confined to the surface of the paraxial mesoderm despite the
presence of Fibronectin and its primary Integrin receptors throughout the tissue.
Fluorescence cross correlation spectroscopy (FCCS) in live embryos revealed a protein
complex containing Integrin 5 and Cadherin 2 and genetic experiments indicate that this
complex represses Fibronectin matrix assembly within the mesenchyme of the paraxial
mesoderm. On the surface of the paraxial mesoderm, Integrin 5 is de-repressed and
Fibronectin matrix coats the tissue surface. Aim 1 is to define the role of Integrin V, the
other main Fibronectin receptor, in this process using FCCS and genetic mosaics. In
addition, fluorescent timer fusion proteins are used to reveal the patterns of adhesion protein
turnover in vivo, and a FRET/FLIM assay is used to examine Integrin conformation in live
embryos. Aim 2 is to identify other components of this protein complex using co-IP and
Mass Spectroscopy. These proteins will be further characterized by in vivo FCCS, gene
knockout and systems analysis of cell motion in the mutants.

## Key facts

- **NIH application ID:** 10146440
- **Project number:** 5R01HD092361-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SCOTT A HOLLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,375
- **Award type:** 5
- **Project period:** 2017-09-05 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146440

## Citation

> US National Institutes of Health, RePORTER application 10146440, The cross-scale biomechanics of tissue morphogenesis (5R01HD092361-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146440. Licensed CC0.

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