PHYSICAL PROPERTIES OF THE EXTRACELLULAR MATRIX

PRESENTED BY FELIX CHIBUZO OBI (20144610)BIOMEDICAL ENGINEERING, MSc

Email: felix4excel@yahoo.com

SUPERVISED BY ASSO. PROF. TERIN ADALI

FACULTY OF ENGINEERINGDEPARTMENT OF BIOMEDICAL

ENGINEERING

Presentation Outline• INTRODUCTION

• PHYSICAL STRUCTURES OF THE EXTRACELLULAR MATRIX

• COMPOSITION OF THE EXTRACELLULAR MATRIX.

• MACHANICAL PROPERTIES OF THE EXTRACELLULAR MATRIX

• CONCLUSION

• REFERENCES

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INTRODUCTION Extracellular Matrix (ECM) are collection of extracellular

molecules secreted by cells that provides structural and biochemical support to the surrounding cells. They are substances containing Collagen, Elastin, Proteoglycans, Glycosaminoglycans and fluid produced by the cells they are embedded. They fill the spaces between the cells in a tissue protecting them and holding them together. They are the natural support Structures of the cells.  The extracellular matrix may be semifluid or rigidly solid and hard as in bone. Each type of connective tissue in animals has a type of ECM: collagen fibers and bone mineral comprise the ECM of bone tissue; reticular fibers and ground substance comprise the ECM of loose connective tissue; and blood plasma is the ECM of blood. Some common function of the Extracellular Matrix includes cell adhesion; cell-to-cell communication and cell differentiation.PHYSICAL PROPERTIES OF THE EXTRACELLULAR MATRIX, FELIX C. O. 2016 3

PHYSICAL STRUCTURES OF THE EXTRACELLULAR

MATRIX

• They may be semifluid or rigidly solid and hard as in bone.

• They are network of proteins and carbohydrates that surrounds the cells and fill the intercellular spaces.

• They are composed of an interlocking mesh of Fibrous proteins and Glycosaminoglycans (GAGs).

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COMPOSITION OF THE EXTRACELLULAR

MATRIX.• Because multicellularity evolved independently in

different multicellular lineages, the composition of ECM varies between multicellular structures. However, the two main Classes of molecules that make up the Extracellular Matrix are Fibrous Proteins and Proteoglycans, other molecules include Water, Electrolytes and Minerals. These Components are produced and organized by the Cells that are embedded within them. They Fibroblast (Fiber making cells) are commonly charged with this responsibility. There are four principles classes of Fibrous Protein found in the Extracellular Matrix namely; Collagen, Elastin, Fibronectin and Laminin. Proteoglycans are composed of Protein core surrounded by long chains of Starch-like molecules called Glycosaminoglycans (GAG). Let’s take a look at these Molecules.

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COLLAGEN• Collagens are strong

stretch-resistant fibers that provide tensile strength to the tissues. They are the most abundant proteins in the human body and are the principle constituent of the tendons and ligament. They are also known to provide support to the skin and help in wound healing.

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ELASTINS

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Elastin is a stretchy and resilient protein that gives elasticity to the tissues, allowing them to stretch when needed and then return to their original state. They are useful in blood vessels, the lungs, and skin and these tissues contain high amounts of Elastin. They are synthesized by fibroblasts and smooth muscle cells.

FIBRONECTIN

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Fibronectins are glycoprotein that connect cells with collagen fibers in the Extracellular Matrix, allowing cells to move through the Matrix. Fibronectins bind collagen and cell-surface integrins, causing a reorganization of the cell's cytoskeleton to facilitate cell movement. Fibronectins are secreted by cells in an unfolded, inactive form. Binding to integrins unfolds Fibronectin molecules, allowing them to form dimers so that they can function properly. Fibronectins also help at the site of tissue injury by binding to platelets during blood clotting and facilitating cell movement to the affected area during wound healing.

The Human Fibronectin

LAMININ

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Laminins are proteins found in the basal laminae of virtually all animals. They form sheet-like network that serves as the “glue” between dissimilar tissues. They also assist in cell adhesion. Laminins bind other ECM components such as collagens, nidogens, and entactins. Laminin are the principle proteins in the basement membrane. Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest.

PROTEOGLYCANS

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Proteoglycans are a combination of proteins and Glycosaminoglycans. Glycosaminoglycans (GAGs) are carbohydrate polymers and are usually attached to extracellular matrix proteins to form Proteoglycans. Proteoglycans have a net negative charge that attracts positively charged sodium ions (Na+), which attracts water molecules via osmosis, keeping the ECM and resident cells hydrated. Proteoglycans may also help to trap and store growth factors within the ECM.

http://study.com/academy/lesson/extracellular-matrix-function-components-definition.html(The Video: Composition of the ECM)

MACHANICAL PROPERTIES OF THE EXTRACELLULAR

MATRIX The ECM can exist in varying degrees

of stiffness and elasticity, from soft brain tissues to hard bone tissues, the elasticity of the ECM can differ by several orders of magnitude. This property is primarily dependent on collagen and elastin concentration, and it has recently been shown to play an influential role in regulating numerous cell functions.

Cells can sense the mechanical properties of their environment by applying forces and measuring the resulting backlash. This plays an important role because it helps regulate many important cellular processes including cellular contraction, cell migration, cell proliferation, differentiation and cell death (apoptosis).

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As said earlier, Collagen provides tissues with strength and stiffness, which serve to protect them against fracture under an applied force. Collagen in mammalian tendon has a strength of ~0.12 GPa, just one order of magnitude lower than high tensile steel [2,104], and an elastic modulus of ~1.2 GPa, demonstrating substantial material stiffness. The table below summarizes the Mechanical properties of Collagen and Elastin.

CONCLUSION Extracellular Matrix are the natural support structures of

the cell, they are mainly made up of fibrous proteins and Proteoglycans. Of all the molecules in the Extracellular Matrix, Collagen and Elastin play major role in the mechanical properties of the ECM. They assemble into fibrous extracellular networks that fulfill crucial structural and mechanical roles supporting tissue function. These two proteins form cross-linked fibers from monomeric units, but till exhibit remarkably different mechanical properties and mechanisms of mechanical response. The result is a resilient matrix that enables tissues to cope with a range of forces spanning biological relevance.

Due to their impressive suite of mechanical properties, these proteins present a tempting direction for biomedical applications, including wound healing, tissue regeneration, and the rational design of mimetic biomaterials. Such design requires recapitulation of mechanical properties, which necessitates a thorough understanding of the relationship between sequence, structure and assembly as they apply to function.PHYSICAL PROPERTIES OF THE EXTRACELLULAR MATRIX, FELIX C. O. 2016

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REFERENCES Extracellular Matrix: Function, Components & Definition http://study.com/academy/lesson/extracellular-matrix-function-

components-definition.html (Video: downloaded on the 25th January, 2016)  Lisa D. Muiznieks, Fred W. Keeley; Molecular assembly and mechanical

properties of the extracellular matrix: A fibrous protein perspective. journal homepage: www.elsevier .com/locate/bbadis

Wikipedia, the free Encyclopedia; Extracellular matrix https://en.wikipedia.org/wiki/Extracellular_matrix  A.W. Clarke, E.C. Arnspang, S.M. Mithieux, E. Korkmaz, F. Braet, A.S.

Weiss, Tropoelastin massively associates during coacervation to form

quantized protein spheres, Biochemistry 45 (2006) 9989–9996.  Y. Tu, A.S.Weiss, Transient tropoelastin nanoparticles are early-stage

intermediates in the coacervation of human tropoelastin whose aggregation is

facilitated by heparan sulfate and heparin decasaccharides, Matrix Biol. 29 (2010)

152–159.

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T.J. Broekelmann, B.A. Kozel, H. Ishibashi, C.C. Werneck, F.W. Keeley, L. Zhang,R.P. Mecham, Tropoelastin interacts with cell-surface glycosaminoglycans viaits COOH-terminal domain, J. Biol. Chem. 280 (2005) 40939–40947. N. Perrimon, M. Bernfield, Specificities of heparan sulphate proteoglycans indevelopmental processes, Nature 404 (2000) 725–728. D. Gheduzzi, D. Guerra, B. Bochicchio, A. Pepe, A.M. Tamburro, D. Quaglino, S.Mithieux, A.S. Weiss, I. Pasquali Ronchetti, Heparan sulphate interacts withtropoelastin, with some tropoelastin peptides and is present in human dermiselastic fibers, Matrix Biol. 24 (2005) 15–25. W.J. Wu, B. Vrhovski, A.S. Weiss, GlycosaT.J. Broekelmann, B.A. Kozel, H. Ishibashi, C.C. Werneck, F.W. Keeley, L. Zhang,R.P. Mecham, Tropoelastin interacts with cell-surface glycosaminoglycans viaits COOH-terminal domain, J. Biol. Chem. 280 (2005) 40939–40947. N. Perrimon, M. Bernfield, Specificities of heparan sulphate proteoglycans indevelopmental processes, Nature 404 (2000) 725–728.

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