Mechanochemical Modeling of Smooth Muscle Activation

Abstract: Smooth muscle has an important role in several physiological processes, where it regulates the wall tension and the size of hollow organs. In blood vessels, the contraction and relaxation of smooth muscle contribute to the mechanical stability of the vessel wall and determines the diameter. To better understand how the active tone of smooth muscle influences the passive layers of the artery wall and how dysfunctions of the smooth muscle are related to pathologies such as hypertension and vasospasm, a coupled chemomechanical model based on structural studies and contractile behavior was proposed in this thesis. Smooth muscle contraction arises when cross-bridges between the myosin and actin filament cycle, causing sliding of the filaments. The contraction is triggered when myosin is phosphorylated by an influx of intracellular calcium ions, which can be initiated through different excitation-contraction pathways.The proposed model coupled a chemical model, where intracellular calcium ion concentration was related to myosin phosphorylation and the fraction of load-bearing cross-bridges, with a mechanical model which was based on the three-element Hill model. The mechanical model, which described a sarcomeric equivalent contractile unit based on structural observations had been developed and modified in different steps to capture the characteristics of smooth muscle behavior, such as isometric contraction, isotonic shortening velocities and length-tension relationships. The chemical material parameters were fitted to calcium-phosphorylation data found in the literature and the mechanical model was fitted against experiments on swine common carotid media performed at Karolinska Instititet, Stockholm. The final coupled model was implemented into a three-dimensional finite element code to simulate the active tone in a two layered artery exposed to realistic pressure pulses. Simulation results indicated that changes in intracellular calcium amplitudes did not have significant effects while changes in the mean value of the intracellular calcium and in the medial wall thickness had a more significant effect on the mechanical response of the arterial wall.