# A single cell assay for tissue activity

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $161,345

## Abstract

Abstract
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
23-045.
Fluctuations in the active biomechanical properties of cells are understudied, but evidence suggest they play a
critical role in both core physiological processes and in disease. For example, tissue phase transitions, from
elastic- to fluid-like (or jammed to unjammed) are thought to arise in part from increased noise in cell junctional
mechanics. These forces can also result in shedding of cellular material like exosomes. Both of these
processes play a central role in cancer progression, most notably in invasion and metastasis. However, a
major challenge is identifying the specific subcellular origin of these forces and the machinery responsible for
them. For example, studies of tissue fluidization using vertex modeling approaches have defined the necessary
and sufficient geometric changes for tissue fluidization in epithelia. Specifically, active fluctuations in cell
junction length are required for the T1 transitions that change junctional topology and allow cells to diffuse like
a fluid. Actomyosin dynamics can drive these transition in the absence of cell division and apoptosis, but these
models focus on actomyosin activity at apical/lateral interfaces (between cells), but largely ignore more indirect
sources of activity, for example deriving from tractions generated at the basal surface which acts to sheer
lateral and apical cell junctions. By tracking the dynamics of single cells in both normal and transformed
primary human mammary epithelial organoids we see evidence that the activity necessary to fluidize a tissue
derives from interactions between cells and their basal interface at the ECM. At the single cell level, we reason
that this activity manifests as fluctuations in cell tractions, specifically at basal cell-ECM interfaces, and at the
tens of minutes timescale. In this supplemental proposal, we will first develop a platform allowing the
measurement of dynamic cell tractions at the cell-ECM interface which we will apply to single normal and
transformed mammary epithelial cells. Second, we will develop a parallel assay for measuring cell tractions at
the cell-cell interface. We hypothesize that the magnitude of fluctuations at the cell-ECM interface will be
several fold higher than at lateral interfaces, and that the largest fluctuations will occur at the tens of minutes
timescale, consistent with that of junctional fluctuations in intact tissues. Successful development of this assay
will allow us to investigate the impact of mechanical fluctuations in processes spanning tissue fluidization,
cancer cell invasions, and exosome shedding.

## Key facts

- **NIH application ID:** 10831316
- **Project number:** 3U01CA244109-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ANDREI GOGA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $161,345
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831316

## Citation

> US National Institutes of Health, RePORTER application 10831316, A single cell assay for tissue activity (3U01CA244109-04S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10831316. Licensed CC0.

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