# Shear stress-activated synthetic cells for targeted drug release in stenotic blood vessels

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $42,104

## Abstract

PROJECT SUMMARY
Narrowing of critical blood vessels due to thrombosis or embolism is one of the most prevalent heart valve
diseases and the leading cause of death with aging. Their hemodynamic environment significantly changes as
a result, with an increase in shear stress up to >1000 dyne/cm2 in highly constricted vessels compared to 1–70
dyne/cm2 in normal vessels. Since the increased shear stress activates platelets, the vessels become even more
narrow at the stenotic site from the platelet aggregation, leading to a life-threatening stroke or long-term disability.
The current treatment for obstructed vessels is to administer thrombolytic or anticoagulant drugs, but it entails
high bleeding risk as active drugs are distributed throughout the body. Thus, to overcome current limitations, the
goal of this proposal is to develop a synthetic cell system that only releases drugs in constricted vessels where
it exhibits abnormally high shear stress. A synthetic cell is a bilayer membrane structure (e.g., vesicle) that
includes various biomolecules to carry out cell-like behaviors. They are gaining attention in the drug delivery field
as they can present sense-responsive behavior towards the surrounding environment when engineered with
membrane proteins. To develop a shear stress-responsive synthetic cell that can be used for targeted drug
delivery in stenotic blood vessels, we will use the most well-studied bacterial mechanosensitive channels, the
mechanosensitive channel of large conductance (MscL). MscL is a non-selective channel that opens upon an
increase in membrane tension. Our lab is the first group, to our knowledge, to develop synthetic cells using MscL
and successfully demonstrate their function under hypo-osmotic condition. Recent theoretical studies have
shown that the MscL reconstituted in vesicles can also be activated by shear stress when flowing through a
narrowing constriction channel. Our hypothesis is that MscL incorporated in vesicles will be opened under shear
stress by vesicle-shape deformation-driven membrane stretch and release the loaded drugs. We will investigate
MscL activity under shear stress using constricted microfluidic channels in Aim 1. Contributing factors, such as
vesicle size and lipid compositions, will be tuned to understand their effects on MscL response. In Aim 2, we will
examine the potential value of the system in vitro. We will introduce thrombolytic drug-loaded synthetic cells into
microfluidic channels that are constricted with experimentally induced fibrin emboli and monitor the dissolution
of the clots. Successful completion of this work will result in the development of shear stress-responsive synthetic
cells that can locally release thrombolytic or anticoagulant drugs in constricted or stenotic vessels. This work will
further expand the application boundary of the synthetic cell field by utilizing mechanical stimulus-responsive
synthetic cells as drug carriers. Additionally, successful activation of Msc...

## Key facts

- **NIH application ID:** 10983737
- **Project number:** 5F31HL170510-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sung-Won Hwang
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,104
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983737

## Citation

> US National Institutes of Health, RePORTER application 10983737, Shear stress-activated synthetic cells for targeted drug release in stenotic blood vessels (5F31HL170510-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10983737. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*