Biological complexity: the extracellular matrix (Introduction)

by David Turell , Friday, February 17, 2023, 20:10 (645 days ago) @ David Turell

It has complex functions has direct connection with the immune system cellular activities:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/17_february_2023/40...

'The extracellular matrix (ECM) forms a dynamic structure around cells that is essential for the supply of environmental factors, mechanical support, and protection of tissues. It includes components such as fibrillar proteins, glycosaminoglycans (GAGs), proteoglycans, and mucus. The molecular, physical, and mechanical properties of the ECM regulate immune cell mobility, survival, and function. In turn, the immune system maintains and regulates healthy matrix and restores matrix integrity after injury.

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"One function of the ECMis to guide immune cell movement and positioning. T cells, for example, move through sites containing thin ECM fibers in preference to more densely cross-linked collagen matrices, whereas heparan sulfate proteoglycans within the vasculature and tissue parenchyma bind and present chemokines to form gradients that direct cell movement. During inflammation, injury, infection, or even aging, ECM components can be released to act as “danger signals.” Conversely, the breakdown of the ECM by matrix-degrading enzymes can generate immunoregulatory fragments. Critically, because cytokines are often bound to GAGs, ECM changes can regulate cytokine availability or activity.

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"There is increasing evidence that immune cell function is regulated by mechano-sensing receptors such as Piezo1, and these ECM changes have major impacts on immune function. Furthermore, a decline in the activity of the mechanosensing transcriptional activators YAP and TAZ during physiological aging results in failure to down-regulate inflammation. Thus, ECM composition actively regulates immune processes, but immune signals will themselves regulate ECM composition, reflecting an essential bidirectional dialog.

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"One prominent way that the immune system regulates the ECM is through transforming growth factor–b (TGF-b), which promotes myofibroblast differentiation and collagen production and inhibits matrix-degrading metalloproteinases. Furthermore, type 2 cytokines, particularly interleukin-13 (IL-13), have emerged as modulators of ECM quantity and quality, which includes regulating the mucosal barrier. Moreover, direct biophysical interaction with chemokines or cytokines can alter ECM structure and/or function. For instance, CXCL4 (PF4) functions by binding to GAGs rather than by directly binding to chemokine receptors. This can lead to remodeling of the cell surface ECM and signaling through proteoglycans.

"Immune cells control ECM not only through the production of cytokines and chemokines but also by direct synthesis of ECM components and the enzymes that break them down. Enzymatic remodeling of the rigid basement membrane by tissue-infiltrating myeloid cells, for example, can provide routes for lymphocytes to follow. Macrophages, which are pivotal in ECM turnover through receptor-mediated uptake of and degradation of collagen, also produce collagens that may provide templates for tissue remodeling. Neutrophils can pull and carry preexisting matrix from nearby sites to wound beds early in the tissue repair process to reestablish new ECM scaffolds."

Comment: the interlocking activities of cells and the immune system through the extracellular matri x beyond mind boggling. The regulatory complexity will be picked apart bit by bit, but it serves to show us that chance can't create the interlocking system of controls. Such a system must be designed all at once to end up properly coordinated in all its various functions. Irreducible complexity once again.