# Microscope for ultrasensitive measurement of single-molecule interaction and conformation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $289,061

## Abstract

ABSTRACT
Mechanical signals play a critical role in regulating physiological and pathological processes like tissue formation
and maintenance, stem cell differentiation and cancer metastasis. However, the molecular mechanisms by which
mechanical forces induce biological responses are largely unknown. This is primarily due to the lack of
automated, high throughput, high resolution, techniques to explore the relationship between mechanical force,
molecular structure and physiological function. The first goal of this proposal is to develop an ultra-stable,
automated, microscope that can measure interaction forces between single molecules while simultaneously
monitoring their conformation. This instrument, called the Microscope for Ultrasensitive-measurement of Single-
molecule Interaction and Conformation (MUSIC), will integrate an ultra-stable atomic force microscope (AFM)
with fluorescence resonance energy transfer (FRET). As described in our preliminary data, we have already
developed prototype technologies for ultra-stable AFM operation and for integrating single molecule FRET and
AFM methods. The second aim of our proposal is to use MUSIC to determine the biophysical basis by which E-
cadherin, an essential cell-cell adhesion protein that mediates the integrity of all soft tissue, responds to
mechanical force. Based on extensive preliminary data, we hypothesize that E-cadherins bind in multiple
conformations and modulate adhesion by switching between these structures. However, the mechanisms by
which different E-cadherin structures are formed is unknown and direct evidence for their interconversion is
lacking. MUSIC will be used to map out the different adhesive conformations adopted by E-cadherin, measure
their force-induced interconversion and to assign a mechanistic role to individual protein domains in E-cadherin
adhesion. The results of this research will provide a biophysical understanding of how cells interact, attach,
detach and metastasize.

## Key facts

- **NIH application ID:** 9870936
- **Project number:** 5R01GM121885-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Sanjeevi Sivasankar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $289,061
- **Award type:** 5
- **Project period:** 2017-02-01 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870936

## Citation

> US National Institutes of Health, RePORTER application 9870936, Microscope for ultrasensitive measurement of single-molecule interaction and conformation (5R01GM121885-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870936. Licensed CC0.

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