Mechanobiology is the study of how physical forces and changes in mechanical properties of tissues contribute to cell behavior. Cells respond to biomechanical forces within their extracellular matrix niche through mechanotransduction, this process converts extracellular mechanical stimuli to intracellular biochemical signals. As immune cells traverse across multiple tissue types and also into pathophysiological situations, we are interested to determine the possibility of immune cells responding to differences in variations in tissue properties. Thus far, we have determined that dendritic cells and macrophages have distinct responses in collagen matrices of different density, and we now aim to elucidate the mechanisms of immunomechanobiology. We further studied macrophage behavior in the context of atherosclerosis disease whereby progression changes the matrice stiffness.