Matrix Effectors and Cancer

Extracellular matrices (ECMs) are highly dynamic three-dimensional structural meshworks composed of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, elastin, (glyco)proteins, and matrix-degrading enzymes, such as proteases and glycosidases [...]

A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans

Apical extracellular matrices can form protruding structures such as denticles, ridges, scales, or teeth on the surfaces of epithelia. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C. elegans. Transient actomyosin-dependent constriction of the underlying lateral epidermis accompanies deposition of the provisional matrix at the earliest stages of alae formation. Actin is required to pattern the provisional matrix into longitudinal bands that are initially offset from the pattern of longitudinal actin filaments. These bands appear ultrastructurally as alternating regions of adhesion and separation within laminated provisional matrix layers. The provisional matrix is required to establish these demarcated zones of adhesion and separation, which ultimately give rise to alae ridges and their intervening valleys, respectively. Provisional matrix proteins shape the alae ridges and valleys but are not present within the final structure. We propose a morphogenetic mechanism wherein cortical actin patterns are relayed mechanically to the laminated provisional matrix to set up distinct zones of matrix layer separation and accretion that shape a permanent and acellular matrix structure.

Efficient Decellularization by Application of Moderate High Hydrostatic Pressure with Supercooling Pretreatment

Decellularized tissues are considered superior scaffolds for cell cultures, preserving the microstructure of native tissues and delivering many kinds of cytokines. High hydrostatic pressure (HHP) treatment could remove cells physically from biological tissues rather than chemical methods. However, there are some risks of inducing destruction or denaturation of extracellular matrices (ECMs) at an ultrahigh level of HHP. Therefore, efficient decellularization using moderate HHP is required to remove almost all cells simultaneously to suppress tissue damage. In this study, we proposed a novel decellularization method using a moderate HHP with supercooling pretreatment. To validate the decellularization method, a supercooling device was developed to incubate human dermal fibroblasts or collagen gels in a supercooled state. The cell suspension and collagen gels were subjected to 100, 150, and 200 MPa of HHP after supercooling pretreatment, respectively. After applying HHP, the viability and morphology of the cells and the collagen network structure of the gels were evaluated. The viability of cells decreased dramatically after HHP application with supercooling pretreatment, whereas the microstructures of collagen gels were preserved and cell adhesivity was retained after HHP application. In conclusion, it was revealed that supercooling pretreatment promoted the denaturation of the cell membrane to improve the efficacy of decellularization using static application of moderate HHP. Furthermore, it was demonstrated that the HHP with supercooling pretreatment did not degenerate and damage the microstructure in collagen gels.

Meisosomes, folded membrane platforms, link the epidermis to the cuticle in C. elegans

Apical extracellular matrices (aECMs) form a physical barrier to the environment. In C. elegans, the epidermal aECM is the cuticle, composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Damage to the cuticle causes stress responses in the underlying epidermis by a process that is poorly understood. Here, we focus on structures connecting the cuticle to the epidermis, that we term meisosomes. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, filled with cuticle. Before moulting, meisosomes align with the underlying cytoskeleton in between furrows. In collagen mutants lacking furrows, that exhibit a constitutive damage response in the epidermis, meisosomes are smaller and fail to align. A loss of connection between the epidermis and the cuticle is also observed in these mutants, as well as a modification of the biomechanical properties of the skin. Meisosomes are therefore an essential component of the skin, serving as attachment platforms between the cuticle and epidermis. They could also be involved in relaying tensile information from the cuticle to the underlying epidermis as part of an integrated stress response to injury and infection.

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect.

Inherited Proteoglycan Biosynthesis Defects—Current Laboratory Tools and Bikunin as a Promising Blood Biomarker

Proteoglycans consist of proteins linked to sulfated glycosaminoglycan chains. They constitute a family of macromolecules mainly involved in the architecture of organs and tissues as major components of extracellular matrices. Some proteoglycans also act as signaling molecules involved in inflammatory response as well as cell proliferation, adhesion, and differentiation. Inborn errors of proteoglycan metabolism are a group of orphan diseases with severe and irreversible skeletal abnormalities associated with multiorgan impairments. Identifying the gene variants that cause these pathologies proves to be difficult because of unspecific clinical symptoms, hardly accessible functional laboratory tests, and a lack of convenient blood biomarkers. In this review, we summarize the molecular pathways of proteoglycan biosynthesis, the associated inherited syndromes, and the related biochemical screening techniques, and we focus especially on a circulating proteoglycan called bikunin and on its potential as a new biomarker of these diseases.

Characteristics and Preparation of Designed Alginate-Based Composite Scaffold Membranes with Decellularized Fibrous Micro-Scaffold Structures from Porcine Skin

Alginate-based composite scaffold membranes with various ratios of decellularized extracellular matrices could be designed and obtained from porcine skin tissue by using supercritical carbon dioxide fluid technology. Retention of decellularized extracellular matrix (dECM) and scaffold-structure integrity was observed. This work provides a simple and time-saving process for the preparation of biomedical alginate-based composite scaffold membranes with fibrous dECM micro-scaffolds, which were further characterized by Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), and scanning electron microscope (SEM). The introduction of fibrous dECM micro-scaffolds enhanced the thermal stability and provided expected effects on the biological properties of the designed composite scaffold membranes in regenerative applications.

Autonomously Propelled Colloids for Penetration and Payload Delivery in Complex Extracellular Matrices

For effective treatment of diseases such as cancer or fibrosis, it is essential to deliver therapeutic agents such as drugs to the diseased tissue, but these diseased sites are surrounded by a dense network of fibers, cells, and proteins known as the extracellular matrix (ECM). The ECM forms a barrier between the diseased cells and blood circulation, the main route of administration of most drug delivery nanoparticles. Hence, a stiff ECM impedes drug delivery by limiting the transport of drugs to the diseased tissue. The use of self-propelled particles (SPPs) that can move in a directional manner with the application of physical or chemical forces can help in increasing the drug delivery efficiency. Here, we provide a comprehensive look at the current ECM models in use to mimic the in vivo diseased states, the different types of SPPs that have been experimentally tested in these models, and suggest directions for future research toward clinical translation of SPPs in diverse biomedical settings.