A Zipper Network Model of Extracellular Matrix Failure Reveals a New Role for Proteoglycans

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Mechanical failure of soft tissues is characteristic of life threatening diseases, including emphysema and vessel wall aneurysms. Failure occurs when mechanical forces are sufficient to rupture the enzymatically weakened extracellular matrix (ECM). Elastin is an important structural protein of the ECM, and is known to stretch beyond 200% strain before failing. However, ECM constructs and native vessel walls composed primarily of elastin and proteoglycans (PGs) have been found to fail at much lower strains. In this study, we hypothesized that PGs significantly contribute to tissue failure. To test this, we developed a novel Zipper Network Model (ZNM), in which springs representing elastin are organized into long wavy fibers in a zipper-like formation and placed within a network of springs mimicking PGs. Elastin and PG springs possessed distinct mechanical and failure properties. The elastin does not percolate while the PGs can serve as bridges between elastin fibers as well as hinder folding of the fibers via bond-bending. During stretching, elastin fibers first become straight, then start stretching the PG bridges. Simulations using the ZNM showed that the failure of PGs alone reduces the global failure strain of the ECM well below that of elastin and hence digestion of elastin does not influence the failure strain. Network analysis also suggested that elastin determines the peak and failure stress while PGs transmit the load and define the failure strain of the network. Predictions of the ZNM were experimentally confirmed by measuring the failure properties of engineered ECM constructs before and after digestion with trypsin that cleaves the core protein of PGs without affecting elastin. This study reveals a novel role for PGs in the failure mechanics of engineered and native ECM with implications for the design of engineered tissues.