Suprastructures of extracellular matrices: paradigms of functions controlled by aggregates rather than molecules

Extracellular matrices (ECM) not only serve as structural scaffolds in organs and tissues, but also determine critical cellular functions through cell-matrix interactions. These are mediated by cell surface receptors that recognise specific structural features of ECMs and, hence, overall physical properties of the acellular environment. ECM structures are subject to hierarchic organisations, which are tightly adapted to the functions of tissues and organs. Only a few specialised tasks are reserved for isolated ECM macromolecules. Instead, molecular ECM components attain their prominent functions only after polymerising into insoluble suprastructural elements, i.e. fibrils, microfibrils, or networks that, in turn, are assembled into regional tissue structures, such as fibres or basement membranes. As an outstanding feature, most, if not all, ECM suprastructures are co-polymers of more than one molecular species that differ in their identity and relative abundance. Thus, ECM suprastructures are composite biological amalgamates. The analogy to metal alloys refers to structural and functional characteristics of ECM composites, which differ from those of each homo-polymeric aggregate. At the tissue level, biological alloys can themselves be assembled into conglomerates that again assume properties distinct from those of each individual alloy. Nevertheless, most studies in matrix biology solely focus on molecular features and mechanisms. Progress has however been made in identifying principles of interactions within suprastructural elements and their functional consequences. We are now only beginning to understand the impact of suprastructural organisation on the assembly and the functions of whole tissues and many fundamental issues in this almost pristine field await discovery.