Digging into ‘the Rabbit-Hole' of the Extracellular Matrix

Abstract

mentally influence the behavior of cells finally resulting in a pathological vicious circle. The ECM parameters that might provoke a cellular reaction can be manifold: molecular composition, 3-dimensional architecture, fiber size and orientation, topology, stiffness or viscoelasticity, posttranslational modifications or matrix-associated growth factors. Booth et al. [4] demonstrated that, in the human lung, fibroblasts that were reseeded on fibrotic decellularized lung matrices derived from patients with idiopathic pulmonary fibrosis (PF) differentiate into αSMA-expressing myofibroblasts mostly by means of a TGF-β-independent mechanism [4] , i.e. they attribute mechanisms that backfire to the biophysical properties of the ECM rather than to soluble inflammatory and fibrogenic mediators. This finding is supported by several studies in different settings [5–9] . Laurent et al. [10] reviewed the role of soluble mediators in disease, based on aberrant remodeling of the ECM. Wagner et al. [11] recently managed to show that human cells (i.e. bronchial epithelial cells, lung fibroblasts and mesenchymal stem cells), when reseeded on emphysematous decellularized lung scaffolds, did not persist past day 7. In contrast, on normal decellularized lung scaffolds, the same type of cells were found to be viable for up to 28 days in culture. Interestingly, when the same cells were cultured on plasIn its physiological context, the extracellular matrix (ECM) is a complex and highly ordered 3-dimensional meshwork of numerous fibrous and nonfibrous molecules. Its function lies far beyond mere architectural support for the anchorage of a tissue’s cellular components. Biochemical and biophysical cues within the ECM are thought to steer biological processes like tissue homeostasis and morphogenesis as well as cellular differentiation, proliferation, survival and migration [1, 2] . By and large, the ECM is composed of mostly huge and complex macromolecules such as collagens, elastin, proteoglycans, fibronectins and laminins. When analyzing these molecules experimentally, their large size, insolubility and degree of cross-linking pose huge challenges. Nevertheless, attempts to decipher the protein composition of human and mouse ECM in much more detail by combining bioinformatics and in vivo confirmation with mass spectrometry-based proteomic technology have been quite successful, revealing the matrisome of the murine lung [3] . Thus, in future, it will become more and more common to decipher the proteomic composition (‘matrisome signature’) of the ECM by proteomic techniques in physiological and pathological processes. To date, it is still unclear whether instructive cues within the ECM could, along with a plethora of secreted mediators, detriPublished online: December 3, 2014