# Osmotic Properties of Healthy and Degenerated Cell Pericellular Matrix

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $196,953

## Abstract

PROJECT SUMMARY / ABSTRACT
Low back pain (LBP) is the leading cause of disability worldwide, of significant socio-economic importance and
is strongly associated with structural breakdown and degeneration of the intervertebral disc (IVD). Mechanical
loading plays an essential role in maintaining the mechanical integrity of the IVD and multiple other spinal tissues
through regulating biosynthesis of extracellular matrix (ECM) proteins. However, abnormal loading can alter this
mechanical homeostasis and lead to further structural breakdown and degeneration. In this regard,
understanding the magnitude of strains and pressures the cells experience within the tissue and the mechanisms
through which cells sense these signals can provide insights into the regulation of IVD development and
maintenance and inform biologic strategies for potential regeneration.
This project utilizes novel DNA origami biosensors and microscale mass spectroscopy techniques to determine
the role the specialized tissue immediately surrounding the cell, called the pericellular matrix (PCM), plays in
transducing the physiochemical signals that embedded cells experience within the IVD. In particular, the osmotic
environment engendered by the composition of the negatively charged and hydrated ECM within the IVD is an
important physiochemical signal linking tissue loading and cellular metabolism. The PCM differs from the bulk
ECM in its composition with greater concentrations of Perlecan and collagen type VI, which models have
suggested induce greater osmotic pressures than in the bulk ECM. In order to understand how mechanical loads
maintain homeostasis or promote pathophysiology there is a critical need to understand how osmotic pressures
vary spatially in IVD tissue and to quantify the pressure cells experience in situ. We first propose to determine
the minimum detectable ion gradient that novel DNA origami sensors can detect (Aim 1A) and determine if the
sensor function is influenced by hydrostatic pressure (Aim 1B), which can also develop within loaded tissue. We
then propose to utilize laser ablation-inductively coupled plasma-mass spectroscopy (LA-ICP-MS) to measure
the ion concentrations within the PCM and ECM in healthy and degenerated IVD tissue and in cells isolated with
intact PCM (Aim 2A). Finally, we will utilize DNA origami biosensors to examine the dynamic changes in
pericellular ion concentrations under confined compression loading (Aim 2B). Together, these aims define and
evaluate an entirely novel sensor technology to address the role of the PCM in regulating mechanobiology of the
intervertebral disc. A detailed understanding of the magnitude of physiochemical signals that cells experience
within loaded tissue is required into to develop a mechanistic understanding of mechanobiology and will provide
critical insight into the development of regenerative strategies for LBP.

## Key facts

- **NIH application ID:** 9876827
- **Project number:** 1R21AR076611-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Benjamin A. Walter
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,953
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876827

## Citation

> US National Institutes of Health, RePORTER application 9876827, Osmotic Properties of Healthy and Degenerated Cell Pericellular Matrix (1R21AR076611-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9876827. Licensed CC0.

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