Effect of protein unfolding on the mechanical behavior of fibrin network

Blood clots are a leading cause of life-threatening clinical events and contribute significantly to global mortality. As the primary structural component of blood clots, fibrin networks exhibit remarkable plasticity and energy dissipation under mechanical load. Understanding plasticity in fibrin networks and their underlying mechanisms is of great clinical importance for treatments of blood clots, such as mechanical thrombectomy. Here, we identify proteins unfolding within fibrin as the driver of its plasticity and dissipation. During conformational changes of proteins, the biopolymer chain exhibits molecular creep—elongation without stress increase—through sequential domain unfolding. By developing a multiscale framework integrating statistical mechanics with continuum modeling, we demonstrate that this molecular creep propagates hierarchically and ultimately dictates macroscopic network plasticity. Interfilamentous branching is regarded as another contributor to plasticity and is modeled as an entropic spring attached to a fibrin fiber within the framework. Numerical simulations indicate that, compared to molecular creep, the detachment of interfilamentous branching has a limited influence on fibrin plasticity. These predictions align well with experimental data, highlighting that protein conformational change induced molecular creep plays the most significant role in governing the fibrin network’s plasticity under tensile loading. This work establishes a physical mechanism for fibrin plasticity and elucidates the mechanical role of molecular creep in natural fibrous materials.