A MICROSTRUCTURAL DATA DRIVEW MULTISCALE MODEL FOR THE ENZYMATIC DEGRADATION AND REMODELING OF COLLAGEN NETWORKS

摘要

Collagen proteases actively participate in remodeling soft tissues, Recent work has demonstrated that metalloproteinases (MMP) and bacterial collagenases (BC) exhibit strain-dependent degradation kinetics [2]. Ascertaining how such nanoscale degradation shapes collagenous tissues at the macroseale is vital to our understanding of collagen management within tissues. As a first step towards this goal, we have developed a multiscale model for the enzymatic degradation and remodeling of collagen networks. Such a model will be useful in understanding the etiology of diseases related to collagen management (such as arthritis and fibrotic disorders), in simulating soft tissue development, and in helping engineer improved biomimetic tissues. MMP and BC appear to degrade type I collagen fibers loaded in tension at a diminished rate compared to unloaded fibers. The exact mechanism is elusive, but one hypothesis is that a strain-induced conformational change renders monomers resistant to cleavage. Bhole et al. [1] have demonstrated a novel in vitro method to measure radial degradation of reconstituted type 1 collagen fibers by BC. The method uses a microliter-scale reaction chamber to mechanically strain collagen networks while they are immersed in a BC solution. Dynamic changes in fiber diameter are measured via microscopic differential interference contrast (DIC) imaging. Our multiscale model is driven by the microstructural data from [1], The model predicts millimeter-scale mechanical changes in a collagenous material based on the nanoscale degradation of collagen fibers. A strain-dependent kinetic relation determines the decay of fibers over time. The model can also predict macroseale changes in the material based on the radial growth as well as decay of fibers as is hypothesized to occur in living tissue [2].