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Review
. 2022 May 30;16(1):13.
doi: 10.1186/s13036-022-00292-x.

Extracellular matrix dynamics: tracking in biological systems and their implications

Michael Hu  1 , Zihan Ling  1 , Xi Ren  2
Affiliations
Review

Extracellular matrix dynamics: tracking in biological systems and their implications

Michael Hu et al. J Biol Eng. .

Abstract

The extracellular matrix (ECM) constitutes the main acellular microenvironment of cells in almost all tissues and organs. The ECM not only provides mechanical support, but also mediates numerous biochemical interactions to guide cell survival, proliferation, differentiation, and migration. Thus, better understanding the everchanging temporal and spatial shifts in ECM composition and structure - the ECM dynamics - will provide fundamental insight regarding extracellular regulation of tissue homeostasis and how tissue states transition from one to another during diverse pathophysiological processes. This review outlines the mechanisms mediating ECM-cell interactions and highlights how changes in the ECM modulate tissue development and disease progression, using the lung as the primary model organ. We then discuss existing methodologies for revealing ECM compositional dynamics, with a particular focus on tracking newly synthesized ECM proteins. Finally, we discuss the ramifications ECM dynamics have on tissue engineering and how to implement spatial and temporal specific extracellular microenvironments into bioengineered tissues. Overall, this review communicates the current capabilities for studying native ECM dynamics and delineates new research directions in discovering and implementing ECM dynamics to push the frontier forward.

Keywords: Bioorthogonal non-canonical amino acid tagging (BONCAT); Bioprinting; Extracellular matrix (ECM); Lung; Newly synthesized protein; Proteomics; Stable isotope labeling by amino acids in cell culture (SILAC).

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Fig. 1
Fig. 1
The dynamic ECM microenvironment plays key roles in lung organogenesis and pathogenesis. a During murine lung branching morphogenesis, highly sulfated heparin-sulfate proteoglycans (HSPGs) at the mesenchyme surrounding the branching tips act to bind and enrich FGF10 to enable effective activation of FGFR2 on the nearby epithelial cells, promoting epithelial branching towards the desired directions. b During the terminal saccular stage of lung development, the selective deposition of elastin around the existing alveoli drives the formation of new alveolar septa, a process termed as secondary septation. c During the progression of pulmonary fibrosis, excessive secretion, deposition, and abnormal arrangement of collagen leads to lung malfunction and compromised gas-exchange efficiency
Fig. 2
Fig. 2
Technologies for labeling NSPs. a SILAC incorporates isotopes-labeled amino acids, such as arginine, into NSPs. b BONCAT labels NSPs by replacing methionine residues with its azide-bearing analog, such as AHA. c Glycosylation-enabled labeling uses azide-bearing monosaccharide probes to tag glycosylated NSPs during post-translational glycosylation
Fig. 3
Fig. 3
Strategies for proteomic identification of NSPs. a Azide-tagged NSPs labeled via bioorthogonal approaches, such as BONCAT and glycosylation-enabled labeling, can be conjugated to affinity tags (e.g. biotin) via the click chemistry, and affinity-purified free from pre-existing proteins to enable ultrasensitive proteomic detection using MS. b Isotope-tagged NSPs exhibit a specific molecular weight shift compared to their untagged native counterparts (for example, each.13C-Arg tag increases the molecular weight by 6 Da), facilitating the identification of MS peaks corresponding to the labeled NSPs
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