A zipper network model of the failure mechanics of extracellular matrices

Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2009; 106(4):1081-6. DOI: 10.1073/pnas.0808414106
Source: PubMed


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.

Download full-text


Available from: Dimitrije Stamenović,
  • Source
    • "These studies are challenging the long held assumption that lung mechanics can be simply partitioned into contributions from elastin at low volume, and collagen at high volume. Based on compelling evidence that alveolar walls can fail under loading, particularly when the matrix is remodeled (Kononov et al. 2001; Ito et al. 2004; Ito et al. 2005; Ito et al. 2006; Ritter et al. 2009), Suki and colleagues have put forward a compelling hypothesis (Fig. 2B) to explain progressive emphysema based on percolation of sequential alveolar wall rupture (Suki et al. 2005; Bates et al. 2007; Suki and Bates 2008). Together these approaches are building a multilevel hierarchical understanding of lung tissue mechanics, moving toward the ultimate goal of predictive power to understand how molecular perturbations alter lung micromechanics. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung function is inextricably linked to mechanics. On short timescales every breath generates dynamic cycles of cell and matrix stretch, along with convection of fluids in the airways and vasculature. Perturbations such airway smooth muscle shortening or surfactant dysfunction rapidly alter respiratory mechanics, with profound influence on lung function. On longer timescales, lung development, maturation, and remodeling all strongly depend on cues from the mechanical environment. Thus mechanics has long played a central role in our developing understanding of lung biology and respiratory physiology. This concise review focuses on progress over the past 5 years in elucidating the molecular origins of lung mechanical behavior, and the cellular signaling events triggered by mechanical perturbations that contribute to lung development, homeostasis, and injury. Special emphasis is placed on the tools and approaches opening new avenues for investigation of lung behavior at integrative cellular and molecular scales. We conclude with a brief summary of selected opportunities and challenges that lie ahead for the lung mechanobiology research community.
    Journal of Biomechanics 10/2009; 43(1):99-107. DOI:10.1016/j.jbiomech.2009.09.015 · 2.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sectorized multibeam cellular communication systems with dynamic channel assignment to beams is considered. Limitations due to co-channel interference are analyzed. A model for traffic performance is developed using multidimensional birth-death processes. Theoretical traffic performance characteristics such as call blocking probability, channel rearrangement rate and overall carried traffic are determined
    Vehicular Technology Conference, 1998. VTC 98. 48th IEEE; 06/1998
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rupture of a Morse lattice is considered in the present paper. The critical rupture force F cr is found to decrease with the number of particles N as F cr ~ 1/. The partition function is obtained for two states of the lattice – with all equal bond lengths and one broken bond. In the first case an accurate expressions for thermodynamic parameters are obtained, and thermodynamic expressions are derived in the harmonic approximation in the latter case. The analytical predictions are confirmed by extensive MD simulations. Cis-trans isomerization is considered as an example. Volume fractions of trans- and cis-isomers versus number of monomer units N are found depending on the torsion stiffnesses.
    Physics of Condensed Matter 06/2010; 75(4). DOI:10.1140/epjb/e2010-00155-9 · 1.35 Impact Factor
Show more