Matritecture: Mapping the extracellular matrix architecture during health and disease

Reuten, Raphael; Mayorca‐Guiliani, Alejandro E.; Erler, Janine T.

doi:10.1016/j.mbplus.2022.100102

Cited by 9 publications

(3 citation statements)

References 40 publications

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“…Emerging new combinations of domains plays a major role in the evolution of modular organization of proteins, and the emergence of adaptive traits. This phenomenon has been shown to be predominant in the evolution of proteins involved in the extracellular matrix, an interconnected network composed of hundreds of macromolecules that includes the multidomain protein family ADAMTS-TSL [62][63][64][65][66]. Here we investigated the ADAMTS-TSL family in order to identify functional sequence regions in their modular structure based on two widely used methods for functional prediction [67], namely sequence conservation analysis [68] and phylogenomic inference [15].…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

Dennler,

Coste,

Blanquart

et al. 2023

PLoS Comput Biol

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Numerous computational methods based on sequences or structures have been developed for the characterization of protein function, but they are still unsatisfactory to deal with the multiple functions of multi-domain protein families. Here we propose an original approach based on 1) the detection of conserved sequence modules using partial local multiple alignment, 2) the phylogenetic inference of species/genes/modules/functions evolutionary histories, and 3) the identification of co-appearances of modules and functions. Applying our framework to the multidomain ADAMTS-TSL family including ADAMTS (A Disintegrin-like and Metalloproteinase with ThromboSpondin motif) and ADAMTS-like proteins over nine species including human, we identify 45 sequence module signatures that are associated with the occurrence of 278 Protein-Protein Interactions in ancestral genes. Some of these signatures are supported by published experimental data and the others provide new insights (e.g. ADAMTS-5). The module signatures of ADAMTS ancestors notably highlight the dual variability of the propeptide and ancillary regions suggesting the importance of these two regions in the specialization of ADAMTS during evolution. Our analyses further indicate convergent interactions of ADAMTS with COMP and CCN2 proteins. Overall, our study provides 186 sequence module signatures that discriminate distinct subgroups of ADAMTS and ADAMTSL and that may result from selective pressures on novel functions and phenotypes.

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Section: Discussionmentioning

confidence: 99%

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

Dennler,

Coste,

Blanquart

et al. 2023

PLoS Comput Biol

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“…These cytokines strongly affect the expression of hundreds of genes, which may lead to changes in the phenotype and function of vascular cells [4][5][6]. Among the genes affected by these cytokines are genes encoding laminins [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

TNF-a-induced laminin-332 promotes an atherogenic endothelial phenotype

Hayderi,

Zegeye,

Meydan

et al. 2023

Preprint

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Background:Laminins are key components of the basement membranes separating endothelial cells from the underlying tissues. They form complex networks of fibers within the basement membrane to provide structural support and regulate the behavior and function of surrounding cells. In mammals, the products of the five alpha, four beta and three gamma laminin genes are combined to generate 16-18 laminin isoforms, which under physiological circumstances confer some tissue specificity, with alpha 4- and alpha 5-containing isoforms being considered vascular-specific. During inflammation, however, the expression pattern of laminin genes may change, which in turn may affect the behavior of surrounding cells. Objectives: We aimed to investigate the impact of tumor necrosis factor alpha (TNF-a) on laminin gene expression in endothelial cells and examine the impact of TNF-a-induced laminin (laminin-332 or LN332) on endothelial cells’ behavior. Results:TNF-a induces LN332-encoding genes in endothelial cells. Endothelial cells cultured on LN332 display irregular shape and appear loosely connected. These cells acquire lower expression of tight junction protein, claudin-5, elevated expression of leukocyte adhesion molecules and enhanced secretion of chemokines. In addition, cells cultured on LN332 are more adhesive to leukocytes and supernatant from these cells is more attractive for primary monocytes in vitro. Notably, LN332-encoding genes are elevated in human atherosclerotic lesions and correlate with the expression of TNF-a. Conclusions: We demonstrate that TNF-a-induced upregulation of LN332 promotes a pro-atherogenic endothelial phenotype. Elevated levels of LN332-encoding genes in atherosclerotic lesions, correlating with TNF-a, suggest a potential role for LN332 in the pathophysiology of atherosclerosis.

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“…On artificial 2D substrates, it has been widely reported that cancer cells prefer stiffer substrates and, moreover, cause stiffening of the surrounding ECM themselves by means of its chemical modification which in turn reinforce cell growth and invasion [ 9 , 10 , 12 ]. However, the physicochemical properties of artificial substrates significantly differ from that of the native tissue matrices and lack the characteristic 3D architectonics which crucially influences the cells’ behavior [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Cell Type and Biomechanical Properties of Decellularized Mouse Organs Drives Tumor Cell Colonization

Pospelov,

Kutova,

Efremov

et al. 2023

Cells

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Tissue engineering has emerged as an indispensable tool for the reconstruction of organ-specific environments. Organ-derived extracellular matrices (ECM) and, especially, decellularized tissues (DCL) are recognized as the most successful biomaterials in regenerative medicine, as DCL preserves the most essential organ-specific ECM properties such as composition alongside biomechanics characterized by stiffness and porosity. Expansion of the DCL technology to cancer biology research, drug development, and nanomedicine is pending refinement of the existing DCL protocols whose reproducibility remains sub-optimal varying from organ to organ. We introduce a facile decellularization protocol universally applicable to murine organs, including liver, lungs, spleen, kidneys, and ovaries, with demonstrated robustness, reproducibility, high purification from cell debris, and architecture preservation, as confirmed by the histological and SEM analysis. The biomechanical properties of as-produced DCL organs expressed in terms of the local and total stiffness were measured using our facile methodology and were found well preserved in comparison with the intact organs. To demonstrate the utility of the developed DCL model to cancer research, we engineered three-dimensional tissue constructs by recellularization representative decellularized organs and collagenous hydrogel with human breast cancer cells of pronounced mesenchymal (MDA-MB-231) or epithelial (SKBR-3) phenotypes. The biomechanical properties of the DCL organs were found pivotal to determining the cancer cell fate and progression. Our histological and scanning electron microscopy (SEM) study revealed that the larger the ECM mean pore size and the smaller the total stiffness (as in lung and ovary), the more proliferative and invasive the mesenchymal cells became. At the same time, the low local stiffness ECMs (ranged 2.8–3.6 kPa) did support the epithelial-like SKBR-3 cells’ viability (as in lung and spleen), while stiff ECMs did not. The total and local stiffness of the collagenous hydrogel was measured too low to sustain the proliferative potential of both cell lines. The observed cell proliferation patterns were easily interpretable in terms of the ECM biomechanical properties, such as binding sites, embedment facilities, and migration space. As such, our three-dimensional tissue engineering model is scalable and adaptable for pharmacological testing and cancer biology research of metastatic and primary tumors, including early metastatic colonization in native organ-specific ECM.

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Matritecture: Mapping the extracellular matrix architecture during health and disease

Cited by 9 publications

References 40 publications

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family

TNF-a-induced laminin-332 promotes an atherogenic endothelial phenotype

Breast Cancer Cell Type and Biomechanical Properties of Decellularized Mouse Organs Drives Tumor Cell Colonization

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