Biology of the extracellular matrix: an overview

Abstract

The extracellular matrix (ECM) is an intricate network composed of an array of multidomain macromolecules organized in a cell/tissue-specific manner. Components of the ECM link together to form a structurally stable composite, contributing to the mechanical properties of tissues. The ECM is also a reservoir of growth factors and bioactive molecules. It is a highly dynamic entity that is of vital importance, determining and controlling the most fundamental behaviors and characteristics of cells such as proliferation, adhesion, migration, polarity, differentiation, and apoptosis.

Figure 1

Schematic illustration highlighting the dynamic cross-talk between cells and the extracellular matrix (ECM). Cells secrete and remodel the ECM, and the ECM contributes to the assembly of individual cells into tissues, affecting this process at both receptor and cytoskeletal levels. Adhesion-mediated signaling, based on the cells’ capacity to sense the chemical and physical properties of the matrix, affects both global cell physiology and local molecular scaffolding of the adhesion sites. The molecular interactions within the adhesion site stimulate, in turn, the signaling process, by clustering together the structural and signaling components of the adhesome. (From Geiger B, Yamada KM. Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol 2011;3:a005033. Copyright 2014 Cold Spring Harbor.)

Figure 2

Regulation of cell behavior by ECM. The effects exerted on cells by ECM can be differently mediated. The ECM can directly bind different types of cell surface receptors or co-receptors (red, orange, black), thus mediating cell anchorage and regulating several pathways involved in intracellular signaling and mechanotransduction. Moreover, the ECM can act by noncanonical growth factor (cyan) presentation and be remodeled by the action of enzymes (yellow pie), which can release functional fragments (green). (From Gattazzo F, Urciulo A, Bonaldo P. Extracellular matrix: A dynamic microenvironment for stem cell niche. Biochim Biophys Acta 2014;1840:2506–2519. Copyright 2014 Elsevier.)

Figure 3

Hypothetical model of ECM, integrins and transmembrane receptors crosstalk in the stem cell niche. ECM/integrin interaction within the stem cell niche contributes to three main functions: (1) Cell-matrix anchorage, in which integrin-mediated cell adhesion physically anchors the stem cell to ECM proteins. Through these mechanisms, growth factor receptors can be activated by an integrin-dependent mechanism as well. (2) Reservoir for growth factors and morphogens: ECM binding of soluble growth factors and morphogens spatially and temporally controls their interactions with transmembrane receptors. Integrin crosstalk with other receptors regulates signaling (Erk1/2, Akt, SMADs) preserving stemness. (3) Biomechanical stiffness. ECM/integrin interaction senses mechanical forces, leading to cytoskeleton re-organization and stem cell homeostasis. , growth factors and their receptors; , morphogens and their receptors; , extracellular matrix; , α and β integrin subunits; , cytoskeletal filaments; SC: stem cell. (From Brizzi F, Tarone G, Defilippi P. Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol 2012;24:645–651. Copyright 2014 Elsevier.)