# Matrix biophysics and pericyte mechanobiology in (patho)physiological angiogenesis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $555,703

## Abstract

PROJECT SUMMARY
 The long-term arc of this project is expected to engineer vascularization of tissue deficits and advance
treatment of microvascular diseases including myocardial infarction, atherosclerosis, pulmonary arterial
hypertension, aneurysm, peripheral artery disease, bone repair, volumetric muscle loss, diabetic wounds, and
cancer. To achieve this goal, the project will advance our fundamental understanding of how local fibrous
extracellular matrix (ECM) biophysical cues dynamically influence pericytes during neovessel formation. The
role of the endothelial cell in vasculogenesis and angiogenesis is well recognized, yet the pericyte’s full scope
of work is less understood, despite its known essential role in proper vascular development. We made a
surprising observation that pericytes exhibit phenotypic plasticity when they spontaneously assemble into 3D
spheroids and reversibly form and adopt endothelial markers when cultured on native and synthetic fibrous
biomaterials in vitro, but not on 2D substrates. Akin to vasculogenic blood islands, tip cell-like protrusions
sprout and retract from these spheroids comprised of pericytes that transdifferentiate to express endothelial
markers. Other studies by our team revealed that matrix fiber diameter and architecture dictate cell
morphology, the mode and rate of cell migration, cell force exertion, protrusion dynamics, and nuclear shape
associated with heterochromatic rearrangements. These published and preliminary studies gave rise to a
central hypothesis that various matrix biophysical parameters differentially direct neovessel formation by
modulating pericyte migration, contraction, protrusion, and phenotypic plasticity. To test this hypothesis, we will
further develop a nanofiber cell force sensing platform to mimic (patho)physiological ECMs through exquisite
tunable control of ECM fiber biophysical parameters (e.g., diameter, density, alignment). With consideration of
disease-simulating biochemical milieu (e.g., oxygen tension, reactive oxygen species, and inflammatory
cytokines), experiments performed under Aim 1 will identify how matrix biophysical cues alter pericyte
migration, contractility, and protrusion dynamics. Aim 2 experiments will develop the in vitro nanofiber scaffold
system to selectively transplant patterned spheroids in vivo for neovessel formation through engineered control
of pericyte plasticity and transdifferentiation. The project’s translational impact will be novel methods of
controlling microvascular expansion and regression in diseased, damaged, and engineered tissues.

## Key facts

- **NIH application ID:** 10836558
- **Project number:** 5R01HL162822-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Amrinder Nain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $555,703
- **Award type:** 5
- **Project period:** 2023-05-05 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836558

## Citation

> US National Institutes of Health, RePORTER application 10836558, Matrix biophysics and pericyte mechanobiology in (patho)physiological angiogenesis (5R01HL162822-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836558. Licensed CC0.

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