Multiscale insights into thrombus growth and detachment under non-physiological blood flow

Background and objective Flow dynamics play a fundamental role in modulating thrombus evolution, serving as a primary driver for mass transport, cell-protein interactions, and structural stability. While it is well-established that local flow patterns significantly influence thrombus growth and morphological changes, the precise biomechanical mechanisms linking varying flow conditions to the dynamic processes of accumulation and detachment remain to be fully elucidated. This study focuses on the intricate correlation between flow-mediated forces and thrombus stability, aiming to uncover how fluidic environments regulate the multiscale transition from cellular adhesion to macroscopic thrombus formation. Method Based on dissipative particle dynamics and a coarse-grained cell model, this study establishes a mesoscopic-scale model for simulating platelet activation, adhesion, and fibrin formation. The proposed method enables high-resolution numerical simulation of thrombus growth, achieving multi-scale computations spanning protein-cell-thrombus levels. Ultimately, it allows for analysis and prediction of thrombus growth status, compositional changes, and detachment processes during thrombus development. Result By combining microfluidic experiments and multiscale computational method, we systematically elucidated the dynamics of thrombus formation and detachment under non-physiological shear flow conditions. Our results indicate that flow intensity significantly modulates the cellular-to-fibrin ratio within thrombus. Through combined experimental and computational analyses, we identified two distinct thrombus detachment mechanisms: shear-driven boundary fragmentation detachment and pressure gradient-induced internal layer separation via thrombus fissuring. Diverging from traditional views that predominantly implicate fluid shear stress in thrombus detachment, our quantitative assessments reveal that momentum transfer from blood cell collisions is a pivotal factor in the detachment process. This insight highlights the interplay and competition between hydrodynamic and cellular kinetics in thrombus growth evolution.