A Biochemomechanical Model of Collagen Turnover in Arterial Adaptations to Hemodynamic Loading

The production, removal, and remodeling of fibrillar collagen is fundamental to arterial homeostasis, including dynamic morphological and microstructural changes that occur in response to sustained changes in blood flow and pressure under physiological conditions. These dynamic processes involve complex, coupled biological, chemical, and mechanical mechanisms that are not completely understood. Nevertheless, recent simulations using constrained mixture models with phenomenologically motivated constitutive relations have demonstrated a capability to predict salient features of the progression of certain vascular adaptations and disease processes. Collagen turnover is modeled, in part, via stress-dependent changes in collagen half-life, typically taken within the range of 10 – 70 days. By contrast, in this work we introduce a biochemomechanical approach to model the cellular synthesis of procollagen as well as its transition from an intermediate state of assembled microfibrils to mature cross-linked fibers, with mechano-regulated removal. The resulting model can simulate temporal changes in geometry, composition, and stress during early vascular adaptation (weeks to months) for modest changes in blood flow or pressure. It is shown that these simulations capture salient features from data presented in the literature from different animal models.