# Biophysical-based approach for controlling blood vessel structure and function

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $68,610

## Abstract

ABSTRACT
Dysregulation of vascular architecture and function is characteristic of a broad spectrum of pathologies, including
inflammation, cardiovascular diseases, and cancer. Therefore, the ability to control angiogenesis and vessel
remodeling has considerable therapeutic benefit. Blood vessels are lined with a monolayer of tightly joined and
mechanically coupled endothelial cells (ECs) that form the barrier between blood and the surrounding tissue.
In addition, it is well established that fluid mechanical stresses, such as ones associated with intravascular and
transvascular flow, are interpreted by ECs to help form and remodel blood vessels. However, while numerous
mechanotransducers in ECs have been proposed, a detailed, quantitative, and complete model of flow sensing
by ECs that assists in developing a systematic pathway to controlling angiogenesis does not exist. Thus, there
is a significant need for accurately engineered in vitro platforms to systematically study and develop a
comprehensive model of the functional outcomes of fluid stresses on blood vessel architecture. Based on our
preliminary data and previous discoveries, we hypothesize that intravascular shear stress and transvascular flow
impart competing effects in controlling blood vessel remodeling leading to quantifiable changes in angiogenesis
vascular permeability, and interendothelial ultrastructure. By thoroughly assessing these parameters, we believe
that our approach will identify the biophysical signatures of dysregulated vessel architecture that are
characteristic of vascular diseases. Moreover, our goal is to use these biophysical signatures to help design
strategies for controlling pathological angiogenesis and vascular permeability. To meet this goal, we will use an
integrated strategy in which 3-D microfluidic systems that allow control of physiological levels of pressure and
flow conditions and the cell/matrix topology of intact blood vessels will be used in conjunction with high-resolution
microscopy and force spectroscopy with nanoscale devices to determine the physical mechanisms by which fluid
stresses control angiogenesis and vascular permeability. In Aim 1, we will quantify changes in blood vessel
structure and function in response to fluid stresses. In Aim 2, we will measure changes in tension at EC junctions
in response to fluid stresses. In Aim 3, we will develop approaches for suppressing angiogenesis and vascular
permeability by stabilizing EC junctions. Completion of these studies will help establish a new paradigm for
using cellular and subcellular biophysics for controlling angiogenesis and blood vessel remodeling.

## Key facts

- **NIH application ID:** 10075697
- **Project number:** 3R01HL141941-03S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Carlos E. Castro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,610
- **Award type:** 3
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075697

## Citation

> US National Institutes of Health, RePORTER application 10075697, Biophysical-based approach for controlling blood vessel structure and function (3R01HL141941-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10075697. Licensed CC0.

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