Figure 5.

Hypothetical model of the involvement of MMPs in MCT mutability, inferred from data on the compass depressor ligaments (CDLs) of the sea-urchin Paracentrotus lividus. The synthetic MMP inhibitor galardin increases the stiffness of CDLs in all three mechanical states, which suggests that in all three states, there is (a) ongoing MMP activity that has the potential to degrade components already incorporated into existing crosslink complexes and components that have been secreted but not yet incorporated, and (b) ongoing synthesis and release of new crosslink components. MMPs are synthesized and secreted as inactive pro-enzymes, then activated extracellularly by proteolytic removal of the pro-peptide domain. It is envisaged that crosslink components are synthesized and secreted separately, then assembled extracellularly to form functional complexes. The black boxes represent cells, although the three processes do not necessarily occur in different cell-types. The red box represents the process by which MMP-TIMP complexes are removed and degraded. The model assumes that activated MMPs and new crosslink components reach the extracellular environment at a constant rate. It is hypothesized that interfibrillar cohesion is regulated only through changes in the rate at which an endogenous MMP inhibitor (which is assumed to be a TIMP-like molecule) is released into the extracellular environment. In the stiff state, there are high levels of TIMP secretion (1), MMP inhibition, and crosslinking. In the standard state there are intermediate levels of TIMP secretion (2), MMP inhibition, and crosslinking. In the compliant state there are low levels of TIMP secretion (3), MMP inhibition, and crosslinking. Also represented is the possibility that an endogenous inhibitor could function as a component of the crosslink complex (red arrows) and thus have a dual function (which may apply to TIMP-like tensilin). The model also assumes that the production of MMP-TIMP complexes exceeds the rate of removal and degradation of MMP-TIMP complexes, which would account for the finding that there is a positive correlation between the degree of CDL stiffness and total gelatinolytic activity. The components marked with a red asterisk contribute to the gelatinolytic activity of CDLs as quantified by gelatin zymography. (From reference [65], https://doi.org/10.1371/journal.pone.0049016 (accessed on 2 May 2023), under the terms of the CC BY 4.0 license, https://creativecommons.org/licenses/by/4.0, accessed on 2 May 2023).