Chondroitin sulfate proteoglycan modulates the permeability of hyaluronan‐containing coats around normal human mesothelial cells

Heldin, Paraskevi; Suzuki, Masanobu; Teder, Priit; Pertoft, Håkan

doi:10.1002/jcp.1041650107

Cited by 19 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, few quantitative data support this hypothesis (41). For example, there is no accurate spatial map of the endogenous aggregating proteoglycans in the PCM on single living cells.…”

Section: Pcm Maximal Extension Occurs Before Bottlebrush Saturationmentioning

confidence: 95%

“…The local physicochemical environment associated with the PCM is an additional layer worth investigating independently from the ECM that will impact these processes. Previous work has examined the permeability of the cell coat to nanoparticles (18,19,41,(45)(46)(47), the free diffusion of particles in the PCM (18,(45)(46)(47), and quantified the variations in porosity of the PCM using qPEA and optical force probe microscopy (19,41). Here, we use qPEAs to characterize changes in PCM permeability and porosity after it has been saturated with exogenous aggrecan (c ag ¼ 333 mg/mL).…”

Section: Fluorescent Aggrecan Assay Reveals Free Binding Sites In Pcmmentioning

confidence: 98%

See 1 more Smart Citation

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Chang

McLane

Fogg

et al. 2016

Biophysical Journal

View full text Add to dashboard Cite

The hyaluronan-rich pericellular matrix (PCM) plays physical and chemical roles in biological processes ranging from brain plasticity, to adhesion-dependent phenomena such as cell migration, to the onset of cancer. This study investigates how the spatial distribution of the large negatively charged bottlebrush proteoglycan, aggrecan, impacts PCM morphology and cell surface access. The highly localized pericellular milieu limits transport of nanoparticles in a size-dependent fashion and sequesters positively charged molecules on the highly sulfated side chains of aggrecan. Both rat chondrocyte and human mesenchymal stem cell PCMs possess many unused binding sites for aggrecan, showing a 2.5x increase in PCM thickness from ∼7 to ∼18 μm when provided exogenous aggrecan. Yet, full extension of the PCM occurs well below aggrecan saturation. Hence, cells equipped with hyaluronan-rich PCM can in principle manipulate surface accessibility or sequestration of molecules by tuning the bottlebrush proteoglycan content to alter PCM porosity and the number of electrostatic binding sites.

show abstract

“…Yet, few quantitative data support this hypothesis (41). For example, there is no accurate spatial map of the endogenous aggregating proteoglycans in the PCM on single living cells.…”

Section: Pcm Maximal Extension Occurs Before Bottlebrush Saturationmentioning

confidence: 95%

Section: Fluorescent Aggrecan Assay Reveals Free Binding Sites In Pcmmentioning

confidence: 98%

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Chang

McLane

Fogg

et al. 2016

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…The presence of proteoglycans would also act to stiffen a network of hyaluronan by effectively shortening the hyaluronan chain as it wraps around the globular G1 domain [17]. When excess proteoglycan is added to the coat, the pore size of the pericellular matrix is decreased, with particles 0.3 microns or larger excluded [18]. Link proteins stabilize the interaction between hyaluronic acid and proteoglycans [19][20][21] and have been shown to have a shortening effect on the length of hyaluronan that is similar to the proteoglycan [17].…”

Section: Pericellular Matrix Structurementioning

confidence: 99%

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

249

238

View full text Add to dashboard Cite

Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

show abstract

“…These coats 1) are removed by digestion with highly specific hyaluronidase, 2) can be stabilized by the serum-derived protein inter-␣-trypsin inhibitor which interacts with hyaluronan (12)(13)(14), and 3) can be increased in size and reinforced by proteoglycans that bind specifically to hyaluronan (15,16).…”

mentioning

confidence: 99%

Hyaluronan Bound to CD44 on Keratinocytes Is Displaced by Hyaluronan Decasaccharides and Not Hexasaccharides

Tammi¹,

MacCallum²,

Hascall³

et al. 1998

Journal of Biological Chemistry

128

View full text Add to dashboard Cite

Abundant hyaluronan is present between epidermal keratinocytes. However, virtually nothing is known regarding its organization in the limited extracellular space between these cells. We have used metabolic labeling with [ 3 H]glucosamine and [ 35 S]sulfate and a hyaluronan-specific biotinylated probe to study the metabolism of hyaluronan and its localization in monolayer cultures of a rat epidermal keratinocyte cell line. Hyaluronan (ϳ20 fg/cell) was present on the apical and lateral surfaces of the cells in two nearly equal pools, either in patches (ϳ160/cell) or diffusely spread. The hyaluronan in the patches is bound to CD44 as indicated by co-localization with an antibody to CD44, and by displacement with hyaluronan decasaccharides as well as with an antibody that blocks hyaluronan binding to CD44. The inability of hyaluronan oligomers shorter than 10 monosaccharides to displace hyaluronan suggests that CD44 dimerization or cooperative interactions are required for tight binding. The diffuse hyaluronan pool is likely bound to hyaluronan synthase during its biosynthesis.Hyaluronan is well known as a constituent of connective tissue extracellular matrices, but more recent studies have also demonstrated its abundance in stratified squamous epithelia including the epidermis (1-3). In contrast with connective tissue extracellular matrices that contain mixtures of collagens, fibronectins, other multiadhesive glycoproteins, proteoglycans, and hyaluronan, hyaluronan is the only known extracellular matrix macromolecule present in high concentration, ϳ2 mg/ ml, in the small extracellular space between adjacent epithelial cells (keratinocytes) that form the epidermis (4, 5). Additionally, studies of human skin organ cultures have shown that the hyaluronan within the epidermis is rapidly turned over (6), an observation that suggests that the epidermis possesses efficient mechanisms to catabolize hyaluronan that are closely coordinated with its synthesis.Although the coating of keratinocytes by hyaluronan is not generally appreciated, it is widely known that cell types of mesodermal origin (7), including fibroblasts (8), chondrocytes (9, 10), and mesothelial cells (11) display surface coats, often several micrometers in thickness, visualized indirectly as a domain excluding particles such as red blood cells. These coats 1) are removed by digestion with highly specific hyaluronidase, 2) can be stabilized by the serum-derived protein inter-␣-trypsin inhibitor which interacts with hyaluronan (12-14), and 3) can be increased in size and reinforced by proteoglycans that bind specifically to hyaluronan (15, 16).Extracellular hyaluronan is often anchored to CD44, a ubiquitous, abundant, and structurally variable plasma membrane receptor that has a hyaluronan binding domain (17). Smaller amounts of hyaluronan may bind to RHAMM, a receptor involved in cell motility and cell transformation through hyaluronan-dependent signaling involving tyrosine phosphorylation (18). In addition, some cell-surface hyaluronan appears to remain tet...

show abstract

Chondroitin sulfate proteoglycan modulates the permeability of hyaluronan‐containing coats around normal human mesothelial cells

Cited by 19 publications

References 22 publications

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Hyaluronan-dependent pericellular matrix☆

Hyaluronan Bound to CD44 on Keratinocytes Is Displaced by Hyaluronan Decasaccharides and Not Hexasaccharides

Contact Info

Product

Resources

About