# Bioengineering approaches to map mechanotransduction in the living cell

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2024 · $399,896

## Abstract

Project Summary/Abstract
It is well known that stem cell differentiation and cell fate are regulated by mechanical forces and mechanics.
We have reported earlier that cell mechanical properties dictate stress-induced spreading and differentiation in
embryonic stem cells (ESCs). Other reports have also demonstrated the effect of forces on pluripotent stem
cells. However, how force regulates (pluripotent) stem cell differentiation and cell fate at the level of chromatin
remains elusive. This is an important question since the chromatin is the hub of gene transcription and DNA
replication and DNA damage repair, critical for pluripotent stem cell self-renewal and differentiation and cancer
stem cell self-renewal. Our preliminary results chromatin domain stretching but not compression rapidly and
nuclear protein LAP2β mediates force transmission from nuclear lamina to chromatin. In addition, RNA
polymerase II (Pol II) is recruited and elongated in response to stretching but not compression and demethylation
of H3K9me3 is necessary for force-induced gene upregulation. Built on these results, we propose 3 specific aims
to elucidate nuclear mechanobiology mechanisms in the living cells. Aim 1: To determine if chromatin stretching
is necessary for force-induced stem cell differentiation; Aim 2: To test the hypothesis that H3K9me3 and H3K9ac
regulate force-induced pluripotent stem cell gene transcription; Aim 3: To determine if large-strain induced
telomere attrition contributes to transition from normal stem cells to cancer stem cells. Our experimental designs
are rigorous and the likelihood of generating insightful discovery is high. The long-term goal is to develop novel
approaches and strategies to intervene pathological processes like malignant tumors.

## Key facts

- **NIH application ID:** 10913301
- **Project number:** 5R01GM072744-20
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Ning Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,896
- **Award type:** 5
- **Project period:** 2005-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913301

## Citation

> US National Institutes of Health, RePORTER application 10913301, Bioengineering approaches to map mechanotransduction in the living cell (5R01GM072744-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10913301. Licensed CC0.

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