# Spatiotemporal interrogation of molecular mechanobiololgy at the cell-cell interface with nanotechnology tools

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $399,963

## Abstract

Abstract
Juxtacrine signaling mediates cell-cell communications via direct molecular interactions at the signaling
interface, during development, synapse formation and remodeling, immune activities, and tissue formation.
Despite increasing knowledge of these signaling events, little is known about how the juxtacrine receptors
sense and regulate cell signaling in response to the dynamic changes of its surrounding cells. The challenge of
interrogating spatiotemporal dynamics of juxtacrine cell-cell signaling stems from the fact that many juxtacrine
receptors integrate chemical, spatial, and mechanical cues to differentially regulate cell signaling. To
deconstruct and decode the working mechanisms of these receptors with high spatiotemporal complexity, new
technology tools allowing manipulation of the individual cues with different modes of stimulation, while
reporting cellular responses with high spatiotemporal precision. Toward this aim, we previously developed
nanotechnology platforms including monovalent quantum dot (mQD) probes, mechanogenetics, nanoruler
force microscopy (NRFM), and magnetically amplified protein-protein interaction (MAP-I) tools. mQDs report
single molecule trajectories of the targeted receptors, providing its dynamic spatial and diffusion properties
precisely. Mechanogenetics allows us to manipulate chemical, spatial, and mechanical properties of the
targeted receptors, while monitoring cellular responses to the respective cues. NRFM enables us to investigate
force-responsive structural changes of the target receptors, and hence provides important insights into the
mechanism of mechanotransduction. MAP-I allows for ultrasensitive detection of protein-protein interactions
through magnetic amplification, enabling identification of weak protein-protein interactions that have not been
possible with any other technologies. By using these new technologies, here, we propose to investigate the
interaction and signaling dynamics of Notch and Neuroligin, key signaling proteins in development and
synaptic function, respectively. Ultimately, we aim to provide a platform technology for the systematic
investigation of operating principles for a wide range of juxtacrine signaling, accelerating our understanding of
cell-cell communication.

## Key facts

- **NIH application ID:** 9851716
- **Project number:** 1R35GM134948-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Young-wook Jun
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,963
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851716

## Citation

> US National Institutes of Health, RePORTER application 9851716, Spatiotemporal interrogation of molecular mechanobiololgy at the cell-cell interface with nanotechnology tools (1R35GM134948-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851716. Licensed CC0.

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