Extra Cellular Matrix (ECM)"(ECM)"

The Extra Cellular Matrix: ECM

Extra Cellular: outside the cell, which explains where the matrix is located. Matrix: structure made from a network of

interacting components Component:

fibrous proteins and glycosaminoglycans (GAGs) Components of the ECM are produced intracellularly by

resident cells, and secreted into the ECM via exocytosis.

04/19/10

Extracellular matrix (ECM)

Surrounds cell Provides mechanical support Controls the flow of nutrients and signals to the cells Consists of Fibrous: collagen, elastin, fibronectin, laminin Non-fibrous: Proteoglycans and polysaccharides

http://kentsimmons.uwinnipeg.ca/cm1504

The extracellular matrix (ECM) is a collec?on of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells.

Examples of extracellular matrix Sheets of epithelial cells rest on a thin layer of extracellular matrix called a basal lamina. Beneath the basal lamina is loose connec?ve ?ssue, which consists largely of extracellular matrix secreted by broblasts. The extracellular matrix contains brous structural proteins embedded in a gel-like polysaccharide ground substance.

Extracellular components and connec?ons between cells help coordinate cellular ac?vi?es

Most cells synthesize and secrete materials that are external to the plasma membrane

These extracellular structures include: Cell walls of (plants, arthropods and fungi) ECM The extracellular matrix (ECM) of animal cells Intercellular junc?ons

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Extracellular Matrix (ECM)

In plants, the ECM is primarily composed of cellulose. In arthropods and fungi, the ECM is largely composed of chi:n. In vertebrates, the ECM is made of a complex mixture of carbohydrates and proteins (plus minerals in the case of bone).

Cell Walls of Plants

The cell wall is an extracellular structure that dis?nguishes plant cells from animal cells

Prokaryotes, fungi, and some pro?sts also have cell walls

The cell wall protects the plant cell, maintains its shape, and prevents excessive uptake of water

Plant cell walls are made of cellulose bers embedded in other polysaccharides and protein

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Extracellular Matrix (ECM) of Animal Cells

Animal cells lack cell walls but are covered by an elaborate extracellular matrix (ECM)

The ECM is made up of glycoproteins such as collagen, proteoglycans, and bronec:n

ECM proteins bind to receptor proteins in the plasma membrane called integrins

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Bacterial Cell Walls

The rigid cell walls of bacteria determine cell shape and prevent the cell from burs?ng as a result of osmo?c pressure.

Gram-nega?ve bacteria (such as E. coli): - a dual membrane system, - thin cell walls (between inner &outer membranes. Gram-posi?ve bacteria (human pathogen Staphylococcus aureus):

- a single plasma membrane, - surrounded by a much thicker cell wall.

pep:doglycan

The cell walls of eukaryotes (including fungi, algae, and higher plants) are composed principally of polysaccharides. The basic structural polysaccharide of fungal cell walls/exoskeleton of arthropods is chi:n (a polymer of N-acetylglucosamine residues) The cell walls of most algae and higher plants are composed principally of cellulose. Cellulose is a linear polymer of glucose residues, oUen containing more than 10,000 glucose monomers.

Chi?n is a linear polymer of N-acetylglucosamine residues, Cellulose is a linear polymer of glucose.

Model of a plant cell wall

The structure and func?on of cell walls change as plant cells develop. The walls of growing plant cells (called primary cell walls) are rela?vely thin and exible, allowing the cell to expand in size. Once cells have ceased growth, they frequently lay down secondary cell walls between the plasma membrane and the primary cell wall. Such secondary cell walls, which are both thicker and more rigid than primary walls, are par?cularly important in cell types responsible for conduc?ng water and providing mechanical strength to the plant.

Primary and secondary cell walls dier in composi?on as well as in thickness. Primary cell walls: cellulose, hemicelluloses, & pec?ns. Secondary walls (more rigid) : generally lack pec?n and contain 50 to 80% cellulose.

Many secondary walls are further strengthened by lignin, a complex polymer of phenolic residues that is responsible for much of the strength and density of wood

How the cell wall helps coordinate cellular activity

Protects the plant cell

Maintains its shape

Prevents excessive uptake of water

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Extracellular Structures Extracellular matrix (ECM)

-Surrounds animal cells -Composed of glycoproteins and fibrous proteins such as collagen -May be connected to the cytoplasm via integrin proteins present in the plasma membrane

The animal extracellular matrix includes the inters??al matrix and the basement membrane. Inters??al matrix is present between various animal cells (i.e., in the intercellular spaces)-fills spaces between cells

Gels of polysaccharides and brous proteins ll the inters??al space and act as a compression buer against the stress placed on the ECM. Basement membranes are sheet-like deposi?ons of ECM on which various epithelial cells rest- closely associated with cell surfaces

Animal cells - glycoproteins Ex. collagen

ECM cell communication, movement

Extracellular Spaces Extracellular Matrix

Connective Tissue underlying an epithelium Fibroblast, primary cell secreting ECM

Extracellular Matrix Components The extracellular matrix has three major components: - Highly viscous proteoglycans (heparan

sulfate, keratan sulfate, chondroi?n sulfate), which cushion cells

- Insoluble collagen bers, which provide strength and resilience

- Soluble mul?adhesive extracellular matrix proteins (bronec?n, laminin), which bind proteoglycans and collagen bers to receptors on the cell surface

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Components of ECM

Components of the ECM

Collagen Most abundant glycoprotein (about half of the total protein in the

body). Forms strong fibers outside of the cell.

Fibers are embedded in a network made of proteoglycans. Proteoglycans

Collagen fibers are embedded in a network made from proteoglycans. Are another class of glycoproteins that consists of a small core

protein with many carbohydrate chains covalently attached. Large complexes can form when hundreds of proteoglycans become

non-covalently attached to a single long polysaccharide molecule.

Components (cont.)

Fibronectin Glycoprotein that attaches the ECM to the cell itself. Binds to cell surface receptors called integrins, which are

built into the plasma membrane of the cell. Integrins

Cell surface receptor that connects to fibronectin, which attaches to the ECM

Span the membrane and bind on their cytoplasmic side to associated proteins attached to microfilaments of the cytoskeleton.

Transmits changes between the ECM and the cytoskeleton it integrates changes occurring outside and inside the cell.

The dierences between the various types of extracellular matrix result from varia?ons on this general theme. Tendons contain a high propor?on of brous proteins, Car:lage contains a high concentra?on of polysaccharides that form a rm compression-resistant gel. In bone, the extracellular matrix is hardened by deposi?on of calcium phosphate crystals. The sheetlike structure of basal laminae also results from the u?liza?on of matrix components that dier from those found in connec?ve ?ssues.

04/19/10

Extracellular matrix (ECM)

Surrounds cell Provides mechanical support Controls the flow of nutrients and signals to the cells Consists of Fibrous: collagen, elastin, fibronectin, laminin Non-fibrous: Proteoglycans and polysaccharides

http://kentsimmons.uwinnipeg.ca/cm1504

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ECM

Cell survival

Cell differentiation

Cell proliferation

Cell migration

Apoptosis Cell death

Cell shape

Cell growth

ECM plays role in almost each event of cell

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The functions of ECM: 1. Plays important role to the survival, growth, and death of cells. Eukaryotic cells

must attach to ECM for their growth excepting blood cells, that we call as anchorage dependence. For example, epithelial cells will turn to apoptosis if they are separated from ECM. Different ECM will give cell different effects. The proliferation of fibroblast will be quick up on a fibronectin matrix, and slow down on a laminin matrix, but the response of epithelial cells to the matrix is just opposite.

2. Controlls the shape of cell. Cells will be spherical if they grow with ECM separately. A cell can present a different shape if it grow on a different ECM. The mechanism of this regulation is mediated by the receptors on ECM that regulates the cytoskeleton.

3Regulates the differentiation by the interaction between cell and special component of ECM. For example, myoblast (sarcoblast) can keep its original shape on fibronectin, but it will stop its proliferation to differentiate and fuse to myotube.

4Mediates cell migration. ECM can regulate the speed and direction of the migration. Laminin can enhance the migration of tumor cells, and the migration of other cells is dependent on ECM too. This dependence is very important during the embryo development and wounds healing.

So, ECM mediate almost every event in cell and life story.

In bone, for example, a mineralized extracellular matrix is designed to provide support and resist compression. In some cases, the matrix simply lls up the space between dierent types of ?ssue, ensuring that they are kept separate and that their func?ons are not disturbed.

The skin has an extensive extracellular matrix that keeps it elas?c and strong. The skin's matrix also plays an important role in the healing process, as do such structures elsewhere in the body. It can also help to regulate communica?on between cells and the produc?on of certain substances in the body. In addi?on, it provides a framework for cell adhesion, encouraging growth and stable healing.

Depending on the type of extracellular matrix is involved, specic cells may be required to build it. Fibroblasts, for example, secrete the matrix that creates brous connec:ve :ssue, while osteoblasts make new bone. When these cells are disrupted in some way, it can cause serious problems, as the body constantly reabsorbs the substances it makes even as it produces more; if no more is being produced, or the matrix is being overproduced, it can cause health condi?ons.

Bones, muscles, and tendons all have extensive extracellular matrices that allow them to perform a variety of func?ons in the body. Tendons and ligaments have special proteins that allow them to be stretched and contracted so that the body can be moved Bone is made primarily from collagen and mineral deposits, crea?ng a very solid, secure structure.

Summary: interactions cell-ECM Major EC structural protein:

What are the major proteins of the ECM?

Collagens, Proteoglycans, Elastin, Fibronectin, Laminin, Tenascin.

Fig. 6-32

Tight junc:on

0.5 m

1 m

Desmosome

Gap junc:on

Extracellular matrix

0.1 m

Plasma membranes of adjacent cells

Space between cells

Gap junc:ons

Desmosome

Intermediate laments

Tight junc:on

Tight junc:ons prevent uid from moving across a layer of cells

Tight Junctions prevent extracellular fluid from leaking across epithelial cells.

fasten cells together.

allow ions, sugars, amino acids, and other things cells need to pass from cell to cell.

Tight junc?ons can bind cells together into leakproof sheets

Anchoring junctions link animal cells

Gap junctions allow substances to flow from cell to cell

Through plasmodesmata, water and small solutes (and some?mes proteins and RNA) can pass from cell to cell

Fig. 6-31

Interior of cell

Interior of cell

0.5 m

Plasmodesmata

Plasma membranes

Cell walls

When cancers aback the body, one of the things they assault rst is the extracellular matrix in the region where they grow. Cancers secrete certain enzymes that digest the structure, providing a direct link with the ?ssue beneath it and allowing the cancer to metastasize as it breaks up and distributes cells to new regions. Without these enzymes, the cancer would not be able to penetrate the vulnerable ?ssue of the body.

Cancer

Of the deaths abributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolu?on, changes in the composi?on and the overall content of the ECM reect both its biophysical and biological proper?es and these strongly inuence tumour and stromal cell proper?es, such as prolifera?on and mo?lity.

Figure 14.17b The Biology of Cancer ( Garland Science 2007)

Metastasis

Metastasis Definition : the spread of a tumor within the body Metastatic cells factor : 1.less adhesive 2. Can penetrate numerous barriers 3.can invade normal tissues

Where do they go?

Figure 14.42 The Biology of Cancer ( Garland Science 2007)

Metasta:c tropism

The prolifera?on phase is characterized by angiogenesis,neovasculariza?on , collagen deposi?on, granula?on ?ssue forma?on (new connec?ve ?ssue and ?ny blood vessels), epithelializa?on, and wound contrac?on.

Hemostasis: a process which causes bleeding to stop

The matura?on phase: when the levels of collagen produc?on and degrada?on equalize.

Pathologic complications, 2 Excessive formation of repair components:

Excessive granulation tissue Desmoid tumor (aggressive fibromatosis)

Best viewed as low grade neoplasm with stubborn tendency for recurrences