title: A zipper network model of the failure mechanics of extracellular matrices.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ritter
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jesudason
authors.forename: Arnab
authors.initials: A
authors.lastname: Majumdar
authors.forename: Dimitrije
authors.initials: D
authors.lastname: Stamenovic
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Buczek-Thomas
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stone
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nugent
authors.forename: Béla
authors.initials: B
authors.lastname: Suki
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D004548:Elasticity; D004549:Elastin / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry*; D008954:Models, Biological; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D011509:Proteoglycans; D004549:Elastin