The research communities of cell biology and biological chemistry have focused the last years to the space between cells revealing a network of macromolecules essential for structural support, cell migration, adhesion and signaling. Matrix-mediated regulation of the various cell functions has been demonstrated during the last decade from the structural biochemical and molecular cell biology studies in various in vitro and in vivo models. It is well known that mutations and structural alterations of matrix molecules are closely related to the development of common diseases, such as cardiovascular disease, cancer including metastasis, and diseases affecting the musculoskeletal system as well as more rare conditions. Upon interactions in the extracellular space, these macromolecules affect the extracellular matrix (ECM) dynamics and via cell receptors communicate with the cellular compartment.