A zipper network model of the failure mechanics of extracellular matrices Export

@article{citeulike:4043414, abstract = {10.1073/pnas.0808414106 Mechanical failure of soft tissues is characteristic of life-threatening diseases, including capillary stress failure, pulmonary emphysema, and vessel wall aneurysms. Failure occurs when mechanical forces are sufficiently high to rupture the enzymatically weakened extracellular matrix (ECM). Elastin, an important structural ECM protein, 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 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. 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 suggested that whereas PGs drive the failure process and define the failure strain, elastin determines the peak and failure stresses. Predictions of the ZNM were experimentally confirmed by measuring the failure properties of engineered elastin-rich ECM constructs before and after digestion with trypsin, which cleaves the core protein of PGs without affecting elastin. This study reveals a role for PGs in the failure properties of engineered and native ECM with implications for the design of engineered tissues.}, author = {Ritter, Michael C. and Jesudason, Rajiv and Majumdar, Arnab and Stamenovi\'{c}, Dimitrije and Buczek-Thomas, Jo A. and Stone, Phillip J. and Nugent, Matthew A. and Suki, B\'{e}la}, citeulike-article-id = {4043414}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0808414106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/4/1081.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/4/1081.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19144920}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19144920}, day = {27}, doi = {10.1073/pnas.0808414106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {cell\_wall}, month = {January}, number = {4}, pages = {1081--1086}, posted-at = {2009-02-13 13:43:10}, priority = {2}, title = {A zipper network model of the failure mechanics of extracellular matrices}, url = {http://dx.doi.org/10.1073/pnas.0808414106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4043414 L3 - citeulike-article-id:4043414 N2 - 10.1073/pnas.0808414106 Mechanical failure of soft tissues is characteristic of life-threatening diseases, including capillary stress failure, pulmonary emphysema, and vessel wall aneurysms. Failure occurs when mechanical forces are sufficiently high to rupture the enzymatically weakened extracellular matrix (ECM). Elastin, an important structural ECM protein, 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 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. 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 suggested that whereas PGs drive the failure process and define the failure strain, elastin determines the peak and failure stresses. Predictions of the ZNM were experimentally confirmed by measuring the failure properties of engineered elastin-rich ECM constructs before and after digestion with trypsin, which cleaves the core protein of PGs without affecting elastin. This study reveals a role for PGs in the failure properties of engineered and native ECM with implications for the design of engineered tissues. IS - 4 JF - Proceedings of the National Academy of Sciences EP - 1086 TI - A zipper network model of the failure mechanics of extracellular matrices VL - 106 SP - 1081 KW - cell_wall AU - Ritter, Michael AU - Jesudason, Rajiv AU - Majumdar, Arnab AU - Stamenović, Dimitrije AU - Buczek-Thomas, Jo AU - Stone, Phillip AU - Nugent, Matthew AU - Suki, Béla PY - 2009/01/27/ UR - http://dx.doi.org/10.1073/pnas.0808414106 ER -