# Defining Mechanical Landscapes at Cell-Cell Junctions

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2020 · $387,170

## Abstract

PROJECT SUMMARY
Mechanical forces play fundamental roles in many intrinsic and collective cellular processes, including tissue
regeneration, morphogenesis, and tumor metastasis. While extensive studies have focused on the forces
between cells and extracellular matrices, mechanical interactions among individual cells appear to be
important yet poorly characterized. These intercellular forces are known to be critical during wound healing,
cancer cell invasion, and other developmental and homeostatic processes. However, the molecular principles
that govern these finely balanced mechanotransduction events are still poorly understood. To depict the
mechanisms of these collective cellular processes, it is essential to measure intercellular forces and correlate
the determined mechanical landscapes with the specific molecular machineries that regulate cellular signaling.
Our lab have proposed precise and easy-to-use DNA-based sensors to visualize and quantify intercellular
forces. We and others recently developed an efficient lipid-based approach to anchor designer DNA
sequences onto the external surfaces of mammalian cell membranes. By employing this approach,
membrane-anchored DNA probes allow sensitive imaging of a broad range of molecular forces at cell-cell
junctions. Current mechanobiology studies are based on techniques typically performed in only a few
specialized laboratories. The proposed sensors are compatible with readily accessible fluorescence
microscopes, highly robust and versatile, and easy to prepare and use. To further develop and adapt these
sensors to study intercellular mechanosensitive events, the future research plan is to: (1) engineer and
optimize DNA-based tensile and compressive force sensors to measure a broad range of intercellular forces at
the single-molecule level. (2) Use well-characterized cadherin-based mechanotransduction as an example,
quantify and monitor forces at cell-cell junctions during collective cell migrations and neural plate shaping. (3)
Apply these sensors to investigate the mechanical roles of Notch activation in immune cell activation. Notch
signaling is highly conserved in different developmental and disease processes. Intercellular ligand-induced
mechanical forces are required in Notch activation. Dependent on the environmental and mechanical context,
Notch activation can have contrary effect in the regulation of tissue growth and immune responses. Our
results will provide unique insights to elucidate the mechanical mechanisms of Notch signal activation.
Our long-term goal is to make intercellular force measurements widely implemented in life science laboratories.
These novel sensors will be broadly used to understand the basic mechanical principles of development,
physiology, and disease, which will also serve as the critical foundation for developing novel strategies in
tissue engineering, regenerative medicine, and cell therapy.

## Key facts

- **NIH application ID:** 10003365
- **Project number:** 5R35GM133507-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Mingxu You
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,170
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003365

## Citation

> US National Institutes of Health, RePORTER application 10003365, Defining Mechanical Landscapes at Cell-Cell Junctions (5R35GM133507-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10003365. Licensed CC0.

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