# Development of a mechanosensitive synthetic cell for mediating intercellular communication.

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $270,490

## Abstract

Project Summary
Our abilities to engineer synthetic cell systems that can communicate with living cells remain limited. The
long-term goal is to engineer cell-like systems with increasingly complex biomimetic functions that can serve
as cell replacement or augment functions of natural cells. The objective of this proposal is to develop a
mechanosensitive synthetic cell that can respond to an increase in shear stress, which is most prevalent in
the cardiovascular system, and secrete bioactive molecules to effect living cells. Cells in our bodies
constantly sense and respond to microenvironmental stimuli, including passive and active physical stimuli,
such as extracellular matrix rigidity, adhesive ligand density, tension, compression, and fluid shear flow. The
rationale underlying this proposal is that completion will result in a novel biomimetic cell-like system as a
novel shear stress-responsive ‘material’ that can interface with natural living cells. The majority of
engineered biomaterials respond to differences in the biochemical environment (e.g. differences in redox,
pH, and enzyme composition) between normal and diseased tissues. By comparison, there has been
relatively less effort in exploiting forces for stimulus-responsive behaviors. The synthetic cell idea is inspired
by natural platelets’ ability to bind and respond to elevated shear stress and secrete granule contents when
bound to a surface. The proposed work consists of three specific aims: 1) Characterize shear stress
response of mechanosensing vesicles, 2) Couple mechanosensing with exocytosis in synthetic cells, 3)
Test intercellular communication of shear stress-activated synthetic cells with endothelial cells in vitro. We
will pursue these aims using an innovative approach of repurposing mechanosensitive channel for shear
stress sensing and using peptide-based membrane fusion. Our lab was the first group to demonstrate
mechanosensing synthetic cells and we have significant expertise in bottom-up synthetic biology. The
proposed research is significant, because it will be the first synthetic cell system developed to communicate
with mammalian cells using calcium-triggered secretion. The work will develop fundamental strategies for
coupling mechanosensing to a biochemical response in synthetic cells. This will open new avenue for other
researchers interested in developing more complex cell-like systems. The results will have an important
positive impact immediately because it will support the idea that mechanosensitive channels can sense
lateral membrane tension due to shear stress and long-term because they lay the groundwork of
engineering synthetic cells with other sensing abilities.

## Key facts

- **NIH application ID:** 10396123
- **Project number:** 5R01EB030031-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Allen Po-Chih Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $270,490
- **Award type:** 5
- **Project period:** 2020-09-02 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396123

## Citation

> US National Institutes of Health, RePORTER application 10396123, Development of a mechanosensitive synthetic cell for mediating intercellular communication. (5R01EB030031-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10396123. Licensed CC0.

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