# Regulation and function of region-specific tissue mechanical properties in epithelial folding

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2021 · $408,098

## Abstract

During embryogenesis, the formation of complex tissues and organs are usually driven by
remodeling of epithelial cells. Epithelial morphogenesis is an intrinsically mechanical process
dictated by forces and the mechanical properties of tissues. Despite significant progress in
deciphering the genetic and biochemical determinants of force generation, little is known about
how tissue mechanical properties are regulated and how this regulation contributes to
morphogenesis. Using Drosophila gastrulation as a model, our recent work reveals that the
collective cell shape changes underlying apical constriction-mediated mesoderm invagination
are dictated by region-specific mechanical properties of the tissue. The tissue interior behaves
as a viscous continuum and flows as the cells constrict apically, thereby mediating the apical-
basal lengthening of the cells. In contrast, the subsequent tissue invagination is contingent on
the rigidity of the apical surface of the flanking, non-constricting cells. The mechanical properties
inherent to the tissue interior and surface are controlled by proteins that regulate cell membrane
expansion and cell polarity, respectively. Disruption of these proteins affects specific aspects of
tissue folding. In the proposed study, we will use a multipronged approach combining genetics,
quantitative live-imaging, biophysics and computer modeling to (1) identify the cellular
mechanisms that facilitate viscous deformation of cells in the tissue interior and (2) determine
how the rigidity of the tissue surface is regulated and how flanking cells contribute to tissue
invagination. To facilitate our work, we have developed biophysical approaches to probe tissue
mechanical properties in vivo and optogenetic tools to control protein activities with high
spatiotemporal precision. Successful completion of our research goals will advance scientific
knowledge by identifying cellular mechanisms that define region-specific mechanical properties
and pinpointing their role in coherent tissue deformation. Moreover, our findings will shed light
on the fundamental regulatory networks that govern how tissues sense and respond to
mechanical forces underlying a variety of developmental and physiological processes.

## Key facts

- **NIH application ID:** 10201655
- **Project number:** 5R35GM128745-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Bing He
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,098
- **Award type:** 5
- **Project period:** 2018-07-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201655

## Citation

> US National Institutes of Health, RePORTER application 10201655, Regulation and function of region-specific tissue mechanical properties in epithelial folding (5R35GM128745-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201655. Licensed CC0.

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