Building basement membranes with computational approaches

Abstract

Basement membranes (BMs) are dense extracellular matrix scaffolds that support cells. Their composition, structure and dynamic regulation are vital for tissue health and altered in human disease. The expansion of experimental and analytical techniques has generated large multiomic datasets that include BM components; however, the organising principles of BM component assembly and the regulation of BMs remain poorly understood. There are over 160 curated BM proteins, including core, ubiquitous components such as type IV collagen and laminin isoforms, as well as tissue-restricted components, and there is increasing experimental evidence of BM protein-protein interactions. Here we describe and compare multiomic, protein-protein interaction, and BM curation databases and discuss the application of systems biology approaches including network analysis, Boolean networks and Ordinary Differential Equations to integrate data and model BM organisation. Applying computational modelling strategies to BM datasets may reveal unknown organising principles of BM assembly and regulation and predict mechanisms of dysregulation in BM-associated diseases.