Atherosclerosis precipitates sequelae such as angina, heart attack and stroke, among others, and therefore is heavily involved in the leading causes of death in the western world. During atherosclerotic lesion formation, leukocytes, fatty substances, cholesterol crystals, cellular waste, calcium, platelets and fibrinogen accumulate in and on the intima and media of arteries, resulting in arterial wall thickening and subsequently continuous narrowing of the vessel lumen. Atherosclerotic plaque may rupture and expose its thrombogenic contents to the blood stream, leading to massive local blood coagulation and formation of a thrombus. Such thrombosis may lead to local and/or distal obstruction of blood vessels and gives rise to a major part of acute coronary deaths worldwide. The mechanical impact from blood flow and pressure imposed on the artery wall during atherosclerosis progression, its consequences on plaque composition and inflammation as well as the process of lesion formation with its interplay with biomechanical conditions, however, remain to be conclusively addressed. In this project, a multiscale and multidisciplinary approach to the mechanobiology of atherosclerosis is taken that is based on computational techniques and experimental calibration and verification as well as in vivo molecular imaging. The biological processes involved take place at the (sub)cellular length scale and will be studied in low density lipoprotein-receptor deficient mice by means of immunohistochemistry, staining for inflammatory cell types and mediators. Serial histology slices will be registered to hybrid fluorescence molecular tomography/x-ray computed tomography images, which will allow to assess the regional distribution of involved cell types and molecular mediators. Based on the imaged 3D geometries, macroscopic computational fluid-solid interaction models with transport and diffusion of species and cells supply an understanding of the local mechanical conditions which can then be correlated to the biological findings. Including a longitudinal study of lesion formation will then allow to formulate hypotheses of functional relationships in the mechanobiology of atherosclerosis. A computational microscopic biological model will be implemented in a stochastic cellular potts model which will be coupled to the macroscopic continuum representation of the region of interest in a multiscale framework. Imaging of several stenoses in mice as well as carefully designed in vitro experiments are applied to test the hyphotheses of the model, calibrate its behavior and evaluate its predictive capabilities.