# In vivo analysis of mechanotransduction

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2020 · $334,588

## Abstract

In vivo analysis of mechanotransduction
Cells in biological tubes must integrate biochemical and mechanical cues in order to expand or
contract in a coordinated manner. Inappropriate responses to changing states underlie
conditions such as heart disease, hypertension and asthma. Despite insights from biophysics
and from cell biology on engineered substrates, many important questions remain regarding
how mechanical information is sensed by cells, translated into biochemical signals, and
integrated to produce a coordinated tissue-level response. For example, how is multicellular
contractility regulated in space and time? How are the induction and propagation of biochemical
signals regulated by mechanical cues? How do different cell types within a tissue coordinate
their actions? To address these questions, we have developed an in vivo model, the C. elegans
spermatheca, which is a tubular tissue in the nematode reproductive system comprised of 24
smooth-muscle-like cells that connect to the uterus via a toroidal valve. The major advantages
of this system are that the cells are naturally stretched and contract as oocytes enter, and are
amenable to quantitative live imaging and targeted genetic manipulation, enabling observation
and manipulation of individual cells in the context of an intact tissue. We have discovered that
oocyte entry induces Ca2+ pulses that sweep across the tissue, culminating in a coordinated
contraction that pushes the fertilized embryo into the uterus. Ca2+ release and contractility in the
spermatheca and valve are coordinated such that while the spermathecal bag contracts, the
valve dilates to allow exit of the fertilized embryo. Well-conserved gene networks regulate these
processes, suggesting broad applicability of our findings to other contractile systems. Here, we
propose a combination of 4D imaging of genetically-encoded biosensors, proteomics, molecular
genetics, and modeling to elucidate the mechanisms which coordinate Ca2+ signaling in
response to stretch. Specifically, we will 1) test the hypothesis that the heterotrimeric G protein,
Gαs, signals through PKA to regulate spermathecal contractility; 2) model the mechanisms by
which stretch triggers calcium release and signal propagation; and 3) determine how valve
contractility is regulated, both autonomously and via communication from the spermathecal bag.
This research will lead to important advances in our understanding of the fundamental
mechanisms by which cells convert mechanical information into biochemical signals, and how
this signaling is integrated to regulate tissue function.

## Key facts

- **NIH application ID:** 10052304
- **Project number:** 2R01GM110268-05
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Erin Jean Cram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,588
- **Award type:** 2
- **Project period:** 2014-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052304

## Citation

> US National Institutes of Health, RePORTER application 10052304, In vivo analysis of mechanotransduction (2R01GM110268-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10052304. Licensed CC0.

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