# Mechanisms and Functions of Unconventional Intercellular Calcium Waves in Electrically Non-excitable Cells

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2023 · $362,560

## Abstract

Project Summary
Mechanotransduction is the process by which cells sense and transduce extracellular mechanical stimuli into
intracellular signaling and gene expression. Mechanotransduction is ubiquitous across diverse organisms and
has significant influences on cell function and behavior, in parallel with chemical and genetic signal transductions.
The mechanics of microenvironments mediate mechanotransduction through cell-microenvironment interactions
and its mis-regulation is at the heart of various pathologies. A major knowledge gap in the field is how mechanical
stimuli from microenvironments are transduced into cellular signaling and what the relationships are between
microenvironmental mechanics, cell signaling, gene expression, and cell functions. We recently discovered that
multiple electrically non-excitable epithelial cell lines can initiate and propagate spontaneous long-distance
intercellular calcium waves (ICWs), when cells are cultured in 2D/3D soft microenvironments, but not in stiff
ones. Because calcium regulates a broad range of essential cell functions, our findings uncover an
unprecedented mechanotransduction nexus between microenvironmental mechanics and diverse cellular
signals. We hypothesize that the cellular actomyosin contractility that is regulated by soft microenvironments
(10s kPa) promotes the initiation and propagation of the long-distance ICWs. In this R35 grant, we propose a
cross-disciplinary research program that systematically elucidates this novel mechanotransduction process and
establishes a framework to bridge the knowledge gap. This will be accomplished by leveraging innovative
approaches such as genetically encoded fluorescent calcium sensors, CRISPR imaging, high-throughput cell
selection, and algorithms to pursue two interrelated research themes. The first theme is the identification of
regulatory mechanisms that initiate the calcium waves by active modulations and live-cell imaging of contractility-
associated proteins. The expected results will provide important molecular insights of the link between
mechanotransduction and the ICWs. The second theme is the dissection of mechanisms through which calcium
waves enhance cell migration and achieve biological functions by manipulating ICWs and investigating the full
transcriptome profiles. The results will advance our understanding of the relationships between
microenvironmental mechanics, cell signaling, gene expression, and cell functions. We envision that the
fundamental principles uncovered in this project will apply broadly to various cell systems and physiological
functions. The long-term objective of our research program is to establish a mechanistic foundation of
mechanobiology and promote the creation of therapeutic strategies which leverage these principles. The success
of this proposal will enable my group to embark in a long-term research direction to tackle a variety of critical and
challenging questions regarding the interplay between mechanotr...

## Key facts

- **NIH application ID:** 10714066
- **Project number:** 1R35GM150812-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Xin Tang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $362,560
- **Award type:** 1
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10714066

## Citation

> US National Institutes of Health, RePORTER application 10714066, Mechanisms and Functions of Unconventional Intercellular Calcium Waves in Electrically Non-excitable Cells (1R35GM150812-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10714066. Licensed CC0.

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