Matrix metalloproteinases in a sea urchin ligament with adaptable mechanical properties

PLoS One. 2012;7(11):e49016. doi: 10.1371/journal.pone.0049016. Epub 2012 Nov 16.

Abstract

Mutable collagenous tissues (MCTs) of echinoderms show reversible changes in tensile properties (mutability) that are initiated and modulated by the nervous system via the activities of cells known as juxtaligamental cells. The molecular mechanism underpinning this mechanical adaptability has still to be elucidated. Adaptable connective tissues are also present in mammals, most notably in the uterine cervix, in which changes in stiffness result partly from changes in the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). There have been no attempts to assess the potential involvement of MMPs in the echinoderm mutability phenomenon, apart from studies dealing with a process whose relationship to the latter is uncertain. In this investigation we used the compass depressor ligaments (CDLs) of the sea-urchin Paracentrotus lividus. The effect of a synthetic MMP inhibitor - galardin - on the biomechanical properties of CDLs in different mechanical states ("standard", "compliant" and "stiff") was evaluated by dynamic mechanical analysis, and the presence of MMPs in normal and galardin-treated CDLs was determined semi-quantitatively by gelatin zymography. Galardin reversibly increased the stiffness and storage modulus of CDLs in all three states, although its effect was significantly lower in stiff than in standard or compliant CDLs. Gelatin zymography revealed a progressive increase in total gelatinolytic activity between the compliant, standard and stiff states, which was possibly due primarily to higher molecular weight components resulting from the inhibition and degradation of MMPs. Galardin caused no change in the gelatinolytic activity of stiff CDLs, a pronounced and statistically significant reduction in that of standard CDLs, and a pronounced, but not statistically significant, reduction in that of compliant CDLs. Our results provide evidence that MMPs may contribute to the variable tensility of the CDLs, in the light of which we provide an updated hypothesis for the regulatory mechanism controlling MCT mutability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological* / drug effects
  • Animals
  • Biomechanical Phenomena
  • Dipeptides / pharmacology
  • Elasticity / drug effects
  • Ligaments / drug effects
  • Ligaments / enzymology*
  • Ligaments / physiology
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Matrix Metalloproteinases / metabolism*
  • Mechanical Phenomena*
  • Sea Urchins / enzymology*
  • Sea Urchins / physiology
  • Tensile Strength / drug effects
  • Viscosity / drug effects

Substances

  • Dipeptides
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Matrix Metalloproteinases

Grants and funding

This research received financial support from the Fondazione Cassa di Risparmio delle Provincie Lombarde (CARIPLO Foundation)-advanced Material projects 2009 (Mimesis - Marine Invertebrates Models & Engineered Substrates for Innovative bio-Scaffolds) and from the Portuguese Foundation for Science and Technology (FCT) (SFRH grant BD/40541/2007). This work was also financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the Programa Operacional Factores de Competitividade - COMPETE and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT) in the framework of the project PEst? C/SAU/LA0002/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.