Multi-cell Agent-based Simulation of the Microvasculature to Study the Dynamics of Circulating Inflammatory Cell Trafficking

摘要: Leukocyte trafficking through the microcirculation and into tissues is central in angiogenesis, inflammation, immune response. Although literature rich with mechanistic detail describing molecular mediators of these processes, integration signaling events cell behaviors within a unified spatial temporal framework at multi-cell tissue-level needed to achieve fuller understanding. We have developed novel computational that combines agent-based modeling (ABM) network flow analysis study monocyte homing. A microvascular architecture derived from mouse muscle was incorporated ABM. Each individual represented by an agent simulation. The model calculates hemodynamic parameters (blood rates, fluid shear stress, hydrostatic pressures) throughout simulated network. These are ABM affect transit chemokine/cytokine concentrations. In turn, monocytes respond their local mechanical biochemical environments make behavioral decisions based on rule set independent literature. Simulated give rise emergent leukocyte rolling, adhesion, extravasation. Molecular knockout simulations were performed validate model, predictions extravasation show good agreement independently published corresponding studies.