Dynamic cell-matrix interactions modulate microbial biofilm and tissue 3D microenvironments

Abstract

Microbial biofilms and most eukaryotic tissues consist of cells embedded in a three-dimensional extracellular matrix. This matrix serves as a scaffold for cell adhesion and a dynamic milieu that provides varying chemical and physical signals to the cells. Besides a vast array of specific molecular components, an extracellular matrix can provide locally heterogeneous microenvironments differing in porosity/diffusion, stiffness, pH, oxygen and metabolites or nutrient levels. Mechanisms of matrix formation, mechanosensing, matrix remodeling, and modulation of cell-cell or cell-matrix interactions and dispersal are being revealed. This perspective article aims to identify such concepts from the fields of biofilm or eukaryotic matrix biology relevant to the other field to help stimulate new questions, approaches, and insights.

Figure 1. Cells in tissue and in biofilm adhere to, and are surrounded by, extracellular matrix

Microscopic images of biofilm and eukaryotic cells within extracellular matrix. Confocal fluorescence images of (a) developing mouse salivary gland showing epithelial cells (magenta) and fibronectin in ECM (green); (b) eukaryotic cell (fibroblast, orange) within a 3D collagen matrix (green); inset shows fibroblast-assembled ECM (multiple colors). (c) The EPS matrix (red) creates compartmentalized bacterial microcolonies (green) and heterogeneous microenvironments; (d) bacteria (streptococci) embedded within EPS matrix. Inset shows SEM images of EPS surrounding bacteria and forming a mesh-like structure; the image was pseudo-colored using Adobe Photoshop software for visualization purposes.

Figure 2. EPS matrix and the dynamics of biofilm development

(a) EPS can be deposited directly on a surface for attachment or on microbial cell surfaces to promote the initial adhesion and local accumulation of microorganisms. (b) As the biofilms develops, the EPS produced locally (as well as acquired from the host environment) enmeshes the microorganisms into a diffusion-limiting polymeric matrix. The matrix help microbes to form highly organized cell clusters or aggregates known as microcolonies, which can vary in shape and size. (c,d) In some cases, these clusters can also serve as building blocks to form larger biofilm superstructures. (e) The diagram depicts a cross-section (top-view) of the complex structure of multi-microcolony biofilm architecture found in some biofilms. Close-up view of the microcolony diagram showing densely packed cells tightly associated with matrix components, such as polysaccharides, protein, and eDNA. It is noteworthy that polymer cross-linkers, such as ionic or nucleic acid-binding proteins, can help assemble DNA-DNA or DNA-polysaccharides complexes. The composition and structure of EPS matrix is complex and varies with time, type of microorganisms, and availability of substrates. The matrix helps to create chemical and physical heterogeneity as well as compartmentalized microenvironments. It influences local cellular activity/behavior and competitive or synergistic inter-species (or even inter-cluster) interactions. At later stages (not shown), production of matrix-degrading molecules by a sub-population of microbial cells and localized mechanical instability trigger biofilm breakdown and cell dispersal.

Figure 3. Schematic summary of dynamic cell-matrix interactions in biofilms and eukaryotic systems

Microbial and eukaryotic cells can secrete and remodel the extracellular matrix. The matrix not only surrounds and cements cell together but also organizes cells into a cohesive and functional 3D polymeric network that provides a scaffold for multicellular biological structures and signaling. It provides a dynamic 3D microenvironment where cells can interact bi-directionally with constantly changing chemical and physical cues that modulate morphogenesis, homeostasis, and pathogenesis.