Electrostatic Contribution of the Proteoglycans to the In-Plane Shear and Compressive Stiffness of Corneal Stroma

2010 ◽  
Author(s):  
Hamed Hatami-Marbini ◽  
Peter M. Pinsky
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Electrostatic Interactions ◽  
Corneal Stroma ◽  
Collagen Fibers ◽  
Connective Tissues ◽  
Compressive Stiffness ◽  
Electrostatic Contribution ◽  
Repulsive Forces

The extracellular matrix (ECM) is a fibrous structure embedded in an aqueous gel. The mechanical and electrostatic interactions of the ECM constituents, i.e. collagen fibers and proteoglycans (PGs), define the structure and mechanical response of connective tissues (CTs) such as cornea and articular cartilage. Proteoglycans are complex macromolecules consisting of linear chains of repeating gylcosaminoglycans (GAGs) which are covalently attached to a core protein. PGs can be as simple as decorin with a single GAG side chain or as complex as aggrecan with many GAGs. Decorin is the simplest small leucine-rich PG and is the main PG inside the corneal stroma. It has an arch shape and links non-covalently at its concave surface to the collagen fibrils. It has been shown that while collagen fibers inside the extracellular matrix resist the tensile forces, the negatively charged glycosaminoglycans and their interaction with water give compressive stiffness to the tissue. The role of PGs in biomechanical properties of the connective tissues has mainly been studied in order to explore the behavior of articular cartilage [1], which is a CT with large and highly negatively charged PGs, aggrecans. In order to explain the role of PGs in this tissue, it is commonly assumed that their contribution to the CT elasticity is because of both the repulsive forces between negatively charged GAGs and GAG interactions with free mobile charges in the ionic bath. The electrostatic contribution to the shear and compressive stiffness of cartilage is modeled by approximating GAGs as charged rods [1]. The Poisson-Boltzmann equation is used to compute the change in electrical potential and mobile ion distributions which are caused by the macroscopic deformation.

Material Properties of Porcine Corneal Stroma in Unconfined Compression

2013 ◽  
Author(s):  
Hamed Hatami-Marbini ◽  
Ebitimi Etebu
Keyword(s):  
Extracellular Matrix ◽  
Corneal Stroma ◽  
Swelling Pressure ◽  
Empty Space ◽  
Collagen Fibers ◽  
Necessary Condition ◽  
Internal Stresses ◽  
Connective Tissues ◽  
Polyelectrolyte Gel ◽  
Hexagonal Arrangement

The tensile properties of the cornea have been extensively studied while there are fewer studies on its compressive stiffness. The mechanical properties and structure of the cornea like many other connective tissues are derived from the function and properties of their extracellular matrix. The corneal extracellular matrix, stroma, is a polyelectrolyte gel composed of collagenous fibers embedded in an aqueous matrix. The cornea has two different functions: optical and mechanical. It is the main refractive component of the visual system and it is an effective barrier resisting the deformation caused by external and internal stresses. A necessary condition for corneal optical properties and transparency is the maintenance of a pseudo hexagonal arrangement of the collagen fibers inside the extracellular matrix. This regular arrangement is attributed to the interaction of collagen fibers with the proteoglycans. Under physiological conditions, the proteoglycans are ionized and form a hydrated gel in the empty space between the collagen fibrils by attracting the water and solutes. The interaction of the negatively fixed charges of the proteoglycans with themselves and with the free ions inside the interstitial fluid contributes to the corneal swelling pressure and subsequently to its compressive properties.

scholarly journals LTBP1 promotes fibrillin incorporation into the extracellular matrix

2021 ◽  
Author(s):  
Matthias Przyklenk ◽  
Veronika Georgieva ◽  
Fabian Metzen ◽  
Sebastian Mostert ◽  
Birgit Kobbe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Wide Spectrum ◽  
Extracellular Matrix Protein ◽  
Connective Tissues ◽  
Pathogenic Variants ◽  
Human Pathology ◽  
Fibrillin 1

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.

The extracellular matrix of the developing cornea: diversity, deposition and function*

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 195-205
Author(s):  
J. B. L. Bard ◽  
M. K. Bansal ◽  
A. S. A. Ross
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulphate ◽  
Corneal Stroma ◽  
Experimental System ◽  
Collagen I ◽  
And Function ◽  
20 Nm

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differentiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morphogenesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen I. We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a result implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere. The latter part of the paper describes our current work on chick stromal deposition using corneal epithelia isolated with an intact basal lamina that lay down in vitro ∼3μm-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epithelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more autonomous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibrildiameter distribution are indistinguishable from controls. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deforming their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.

scholarly journals Hemicentin-1 is an essential extracellular matrix component of the dermal–epidermal and myotendinous junctions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Welcker ◽  
Cornelia Stein ◽  
Natalia Martins Feitosa ◽  
Joy Armistead ◽  
Jin-Li Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Developmental Stages ◽  
Cell Types ◽  
Connective Tissues ◽  
Functional Behavior ◽  
Transmission Electron ◽  
Cellular Microenvironments ◽  
And Function ◽  
Myotendinous Junctions

AbstractThe extracellular matrix architecture is composed of supramolecular fibrillar networks that define tissue specific cellular microenvironments. Hemicentins (Hmcn1 and Hmcn2) are ancient and very large members (> 600 kDa) of the fibulin family, whose short members are known to guide proper morphology and functional behavior of specialized cell types predominantly in elastic tissues. However, the tissue distribution and function of Hemicentins within the cellular microenvironment of connective tissues has remained largely unknown. Performing in situ hybridization and immunofluorescence analyses, we found that mouse Hmcn1 and Hmcn2 show a complementary distribution throughout different tissues and developmental stages. In postnatal dermal–epidermal junctions (DEJ) and myotendinous junctions (MTJ), Hmcn1 is primarily produced by mesenchymal cells (fibroblasts, tenocytes), Hmcn2 by cells of epithelial origin (keratinocytes, myocytes). Hmcn1−/− mice are viable and show no overt phenotypes in tissue tensile strength and locomotion tests. However, transmission electron microscopy revealed ultrastructural basement membrane (BM) alterations at the DEJ and MTJ of Hmcn1−/− mice, pointing to a thus far unknown role of Hmcn1 for BM and connective tissue boundary integrity.

Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery

2016 ◽  
Vol 13 (3) ◽  
pp. 819-828 ◽  
Author(s):  
Fengbin Ye ◽  
Stefania Baldursdottir ◽  
Søren Hvidt ◽  
Henrik Jensen ◽  
Susan W. Larsen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Articular Cartilage ◽  
Electrostatic Interactions

scholarly journals The role of matrix metalloproteinases in glaucoma pathogenesis

2015 ◽  
Vol 8 (3) ◽  
pp. 28-43 ◽  
Author(s):  
Inessa Stanislavovna Beletskaya ◽  
Sergey Yurievich Astakhov
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Clinical Investigation ◽  
Experimental Studies ◽  
Glaucomatous Optic Neuropathy ◽  
Connective Tissues ◽  
Activity Impairment ◽  
Extracellular Matrix Components ◽  
The Impact

Matrix metalloproteinases belong to an enzyme family, which assure a proteolysis of practically all components of the extracellular matrix of connective tissues in normal and pathological conditions. At physiological conditions, there are evidences on the impact of this enzyme group in the embryogenesis, morphogenesis, angiogenesis, and tissue involution. The activity impairment of matrix metalloproteinases and of their specific inhibitors leads to the biosynthesis misbalance and to the degradation of extracellular matrix components; it plays a role in the development of such diseases as diabetes mellitus, rheumatoid arthritis, and arteriosclerosis. Laboratory tests and clinical investigation results confirm the role of these enzymes in tissue remodeling of different eyeball structures in glaucoma (in particular, of the trabecular meshwork and the optic disc); it leads to intraocular fluid outflow impairment and to the glaucomatous optic neuropathy development. In the review, the analysis of clinical and experimental studies is performed that are dedicated to the investigation of matrix metalloproteinases role in the pathogenesis of different glaucoma types, of the possibility to use them as biomarkers, as well as therapeutic action targets in this disease.

Influence of Ionic Concentration on Swelling Behavior and Shear Properties of the Bovine Cornea

2012 ◽  
Author(s):  
Hamed Hatami-Marbini ◽  
Ebitimi Etebu
Keyword(s):  
Extracellular Matrix ◽  
Dermatan Sulfate ◽  
Core Protein ◽  
Incident Light ◽  
Corneal Stroma ◽  
Ionic Concentration ◽  
Collagen Fibers ◽  
Collagen Fibrils ◽  
Knock Out ◽  
Free Ions

The mechanical properties and structure of connective tissues such as the cornea and the cartilage are derived from the functions and properties of their extracellular matrix, a polyelectrolyte gel composed of collagenous fibers embedded in an aqueous matrix. The collagen fibers in the extracellular matrix of the corneal stroma are arranged in regular lattice structures, which is necessary for corneal transparency and transmitting the incident light to the back of the eye. This regular pseudo hexagonal arrangement is attributed to the interaction of collagen fibers with the proteoglycans as these regularities are lost in knock-out mice [i]. Proteoglycans (PGs) are heavily glycosylated glycoproteins. They consist of a core protein to which is glycosaminoglycan chains are covalently attached. The main PG in the corneal stroma is the proteoglycan decorin. Decorin is the simplest small leucine-rich PG and only has a single glycosaminoglycan side chain. It has a horse shape core protein and binds collagen fibrils at regular sites. Chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) are among the prevalent glycosaminoglycans found in the cornea. Under physiological conditions, these linear carbohydrate polymers are ionized and carry negative charges due to the presence of negatively charged carboxylate and sulfate groups. Therefore, a hydrated gel is formed in the empty space between collagen fibrils by attracting water. The interaction of negatively charged glycosaminoglycans with themselves and their interaction with the free ions contribute to the corneal swelling pressure and subsequently to its compressive stiffness. From structural view point, the corneal stroma is a composite polyelectrolyte system in which the observed regular spacings of the collagens are suggested to exist because of the structural interaction of collagens, negatively charged glycosaminoglycans, and the free ions in the interfibrillar space.

Pathophysiological Mechanisms Destruction of the Lung Connective Tissue in Tuberculosis

2019 ◽  
pp. 14-20
Author(s):  
O. S. Shevchenko ◽  
I. A. Ovcharenko ◽  
L. D. Todoriko
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Collagen Fibers ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Blood Monocytes ◽  
Pulmonary Tissue ◽  
Α2 Macroglobulin ◽  
The Family ◽  
Pathological Event

Background. The restructuring of the lung tissue stroma during destructive tuberculosis is one of the most important pathological events in the formation of residual changes in the lung tissue during tuberculosis inflammation. Most patients with tuberculosis have destructive forms of this disease. Therefore, studies of pathomorphological changes in the pulmonary tissue of tuberculosispatients are very relevant. It is known that the formation of decavities in volves the destruction of the extracellular matrix, which includes collagen fibers that support the structure of the lungs. The destruction of this matrix leads to the destruction of lung tissue and is a consequence of the activity of proteinase enzymes. One of the products of the destruction of collagen fibers of the lung tissue is oxyproline and its fractions. It has been proventhatin the lungs collagen fibers break down matrix metalloproteinases (MMPs), which belong to the family of proteinases, and are able to affectall component soft he extracellular matrix. The process of MMP synthesis is regulated at the transcription level, and the irproteolytic activity is controlled by proenzymes, as well as inhibition of active enzymes by endogenous inhibitors, α2-macroglobulin and tissue inhibitors of metalloproteinases (TIMP), which play an important role in fibrosis processes. However, it is important not only the level of MMP, but also their ratio with TIMP. An increase in the level of TIMP over MMP leads to the degradation of capillaries of the interalveolar septa, while the predominance of MMP over TIMP leads to the destruction of the component soft he extracellular matrix. Recent studies indicate the role of aldosterone in the processes of fibrosis. It is able to activate blood monocytes, induce in flammation, lead to impaired fibrinolysis. Also aldosterone is able to enhance the synthesis and accumulation of collagen. Elevated levels of aldosterone, stimulating the growth of smooth muscle fibers, contribute to the development of fibrosis in the lungs. There is evidence that aldosterone is able to enhance the degradation of the extracellular matrix through the activation of MMP. Conclusions. Thus, the destruction of the extracellular matrixis one of the most important pathological event sin the formation of residual changes in the lung tissue with tuberculous inflammation.

scholarly journals The role of extracellular matrix in mouse and human corneal neovascularization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
M. Barbariga ◽  
F. Vallone ◽  
E. Mosca ◽  
F. Bignami ◽  
C. Magagnotti ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Medical Condition ◽  
Corneal Stroma ◽  
Acanthamoeba Keratitis ◽  
Corneal Neovascularization ◽  
Collagen Vi ◽  
Tenascin C ◽  
Human Proteins ◽  
Specific Proteins

Abstract Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularized vs healthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.

On Mechanics of Connective Tissue: Assessing the Electrostatic Contribution to Corneal Stroma Elasticity

2009 ◽  
Vol 1239 ◽  
Author(s):  
Hamed Hatami-Marbini ◽  
Peter M. Pinsky
Keyword(s):  
Corneal Stroma ◽  
Unit Cell ◽  
Tissue Elasticity ◽  
The Finite Element Method ◽  
Connective Tissues ◽  
Electrostatic Contribution ◽  
Hexagonal Arrangement ◽  
Collagenous Tissues ◽  
Hierarchal Structure ◽  
And Cartilage

AbstractThe extracellular matrix plays a crucial role in defining the mechanical properties of connective tissues like cornea, heart, tendon, bone and cartilage among many others. The unique properties of these collagenous tissues arise because of both the hierarchal structure of collagens and the presence of negatively charged proteoglycans (PGs) which hold collagen fibers together. Here, in an effort to understand the mechanics of these structures, using the nonlinear Poison-Boltzmann (PB) equation, we study the electrostatic contribution to the elasticity of corneal stroma due to the presence of negatively charged PG glycosminoglycans (GAGs). Since collagens and GAGs have a regular hexagonal arrangement inside the corneal stroma, a triangular unit cell is chosen. The finite element method is used to solve the PB equation inside this domain and to obtain the electric potential and ionic distributions. Having the ion and potential distributions throughout the unit cell, the electrostatic free energy is computed and the tissue elasticity is calculated using the energy method. It is shown that as the ionic bath concentration increases; the electrostatic contribution to tissue elasticity is reduced.

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