Strain-mediated degradation and contact-guided deposition can explain collagen organization in healthy and infarcted myocardium

Understanding mechanobiology-driven cardiac collagen organization is crucial for devising strategies to restore tissue structure and function of diseased hearts. Here, we developed a computational framework that couples a mechanics model of the left ventricle with a mechanobiology-informed model of collagen reorientation to investigate the mechanisms underlying cardiac collagen organization. The framework could replicate physiological left ventricular collagen orientation only when assuming that collagen degradation follows a V-shaped relation with strain. Furthermore, contact guidance between cardiac fibroblasts and collagen fibers emerged as an important mechanism for maintaining collagen orientation and anisotropy. Being aligned with the collagen fibers, cardiac fibroblasts promoted strong collagen anisotropy through deposition in the main direction of the cell. In contrast, increased fibroblast contractility resulted in unphysiological orientations of the cells and therefore misaligned collagen deposition. This suggests that fibroblasts maintain rather than drive the collagen orientation in the healthy heart. In the infarcted left ventricle, however, the same mechanobiological mechanisms that explain physiological collagen organization lead to reorientation of the collagen fibers and reduced anisotropy, which is consistent with literature observations. These findings may contribute to the design of novel targeted therapeutic strategies aimed at restoring myocardial structure-function relationships in diseased hearts.