Fundamentals for modelling the airway wall: Interplay between cells, extracellular matrix, dimensionality, architecture and mechanics in the lung

Our body, organs and tissues are made up of cells that are held together by a sort of glue called the extracellular matrix (ECM). In this three-dimensional environment the cells stick together and to the ECM. Mechanical properties of the ECM such as stiffness determine the fate and function of the bound cells. Therefore, it may come as no surprise that changes in the ECM’s composition and stiffness have an adverse effect on the organ’s function that is composed of the cells. This thesis showed that during chronic obstructive pulmonary disease, a lethal disease without cure, the cross-talk between cells and ECM is disrupted. We developed threedimensional culture models to understand fibroblasts i.e. cells from the connective tissue of main lung and airway cells are affected by ECM from healthy and diseased lungs as well as by varying stiffnesses. As it appears, higher than normal ECM stiffnesses promote airway disease. Our results pave the way for the development of novel therapies to treat COPD by targeting the derailed ECM.