# Allosteric control of collagen fibril degradation by matrix metalloprotease-1

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2023 · $314,000

## Abstract

Project Summary
Collagen, the most abundant human protein, provides a scaffold for cells to maintain tissue and organ integrity.
Fibrillar collagen is highly resistant to proteolysis and is degraded by specific matrix metalloproteases (MMPs).
The degradation of fibrillar collagen is an essential part of tissue remodeling and is involved in many normal and
pathological processes. While the degradation of triple-helical collagen monomers is well-studied, degradation
of native collagen fibrils remains poorly understood. Fibrils are insoluble in physiological buffers, heterogeneous,
and extended substrates, making them challenging to study using standard biochemical assays. We have
overcome these limitations by developing a single-molecule method to track and analyze the motion of labeled
MMPs on fibrils using a home-built total internal reflection fluorescence microscope (TIRFM). We propose to
study the roles of MMP1 and MMP9 in degrading type-1 collagen fibrils. MMP1 can degrade triple-helical
collagen, whereas MMP9 cannot degrade triple-helical collagen significantly. However, MMP9 is upregulated in
numerous skin diseases, cancer metastasis, wound, inflammation, pneumonia, and atherosclerosis. We propose
to study the mechanism of fibril degradation by two important MMPs by a combination of single-molecule
tracking, innovative analysis, simulations, ensemble assays, and animal studies.

## Key facts

- **NIH application ID:** 10853496
- **Project number:** 7R01GM145210-02
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Susanta Kumar Sarkar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $314,000
- **Award type:** 7
- **Project period:** 2022-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853496

## Citation

> US National Institutes of Health, RePORTER application 10853496, Allosteric control of collagen fibril degradation by matrix metalloprotease-1 (7R01GM145210-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10853496. Licensed CC0.

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