Cell–3D matrix interactions: recent advances and opportunities

Tissues consist of cells and their surrounding extracellular matrix (ECM). Cell–ECM interactions play crucial roles in embryonic development, differentiation, tissue remodeling, and diseases including fibrosis and cancer. Recent research advances in characterizing cell–matrix interactions include detailed descriptions of hundreds of ECM and associated molecules, their complex intermolecular interactions in development and disease, identification of distinctive modes of cell migration in different 3D ECMs, and new insights into mechanisms of organ formation. Exploring the roles of the physical features of different ECM microenvironments and the bidirectional regulation of cell signaling and matrix organization emphasize the dynamic nature of these interactions, which can include feedback loops that exacerbate disease. Understanding mechanisms of cell–matrix interactions can potentially lead to targeted therapeutic interventions. The diversity of hundreds of extracellular matrix (ECM) molecules in different tissues and their interactions are now being documented in ‘matrisome’ databases.Physical properties of the 3D ECM, including viscoelasticity and microarchitecture, can govern cell adhesion, mechanotransduction, and multiple modes of cell migration.New advances in ECM biology are identifying mechanisms of cancer progression and fibrosis, as well as potential therapeutic targets.Characterizations of cell–ECM feedback loops and computational modeling are providing new insights and potential opportunities for intervention in diseases and disorders.