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Extracellular Matrix. Cell Biology Lecture 11. Readings and Objectives. Reading Cooper: Chapter 14 Topics The Extracellular Matrix Composition Cell-Matrix Interactions Cell-Cell Interactions. Extracellular Matrix. Introduction Cell walls: bacteria, fungi, algae, and higher plants

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extracellular matrix

Extracellular Matrix

Cell Biology

Lecture 11

readings and objectives
Readings and Objectives
  • Reading
    • Cooper: Chapter 14
  • Topics
  • The Extracellular Matrix
  • Composition
  • Cell-Matrix Interactions
  • Cell-CellInteractions
extracellular matrix1
Extracellular Matrix


Cell walls: bacteria, fungi, algae, and higher plants

Animal cell in tissues embedded in an extracellular matrix of proteins and polysaccharides


Provides structural support to cells and tissues

Important role in regulating cell behavior

Cell to cell interaction, communication

general structure of extracellular matrix
General Structure of Extracellular Matrix

Animal cells embedded in an extracellular matrix

Basal laminae:thin layer on which epithelial cells rest. Also surrounds muscle cells, adipose cells, and peripheral nerves

most abundant in connective tissues

Connective tissue

loose connective tissue




composition of extracellular matrix
Composition of Extracellular Matrix

Fibrous proteins

Polysaccharides- gel like environment

Adhesion proteins- link components of the matrix to one another and to cells

Different matrices have different amounts of each component

Tendons, rich in fibrous proteins

Cartilage, high in polysaccharides

Bone, calcium phosphate crystal deposition

Collagen-major structural fibrous protein

Forms triple helices

Triple helix domains: repeats of the amino acid sequence Gly-X-Y

Glycine in every 3rd position

X=Pro, packs helices closely

Y= hydroxyproline,synthesized in ER

Pro, Hpro stabilizesby helping H-bonding

Matrix composition: Collagen

Type I collagen- the most abundant

polypeptide chains have about 330 Gly-X-Y repeats

Secreted through ER/golgi, form collagen fibrils

Triple helical molecules are associated in regular staggered arrays

Covalent cross-links: lysine and hydroxylysine side chains

strengthen the fibrils

Fibrils form collagen fibers, several µm in diameter

Matrix composition: Collagen

Some are not fibril forming

Fibril-associated collagens: bind to collagen fibrils, link to others or to other matrix components

Network-forming collagens: have non helical interruption, cross-link to network

Anchoring fibrils: link basal laminae to underlying connective tissues

Transmembrane collagens: proteins that participate in cell-matrix interactions

Types of Collagen

Network-forming collagens

Extracellular matrix gels are polysaccharides called glycosaminoglycans(GAGs).

GAGs are repeating units of disaccharides: One sugar is either N-acetylglucosamine or N-acetylgalactosamine, the second is usually acidic (glucuronic acid or iduronic acid).

Matrix Polysaccharides

sulfate groups make GAGs negatively charged

bind positively charged ions and trap water molecules to form hydrated gel

GAGs are linked to proteins to form proteoglycans

Matrix Polysaccharides

Link matrix components

to each other

to cell surfaces

Fibronectin : main adhesion protein of connective tissues

A homodimeric protein (2500 aa/subunit), binds

collagen and GAGs


Recognized by cell surface receptors

Attachment of cells to the extracellular matrix

Matrix Adhesion proteins: Fibronectin

Laminin: adehsion protein of basal laminae

Heterotrimeric: α, β, and γ-chains(5, 4, 3 genes, respectively)

have binding sites for

cell surface receptors, eg integrins

type IV collagen


Assemble to cross-linked network

Linking cells and matrix

Matrix Adhesion proteins: Laminins

cell matrix interactions
Cell-Matrix Interactions

Integrins: major cell surface receptors, involved in attachment of cells to the extracellular matrix

Transmembrane proteins, heterodimer of α and β subunits (18α, 8β)

Bind to short aa in,




also anchor the cytoskeleton to the extracellular matrix

cell matrix junctions
Cell-Matrix Junctions

Two types of cell-matrix junction

Focal adhesions:bundles of actin filaments are anchored to βsubunits of integrins via


Vinculin via talin

Assembly of focal adhesions

Focal complex: small group of integrins

RecruiteTalin, Vinculin, α-actinin and Formin

Formin initiates actin bundles

focal adhesions are reversible
Focal adhesions are reversible

Integrins can reversibly bind matrix components

change conformation between active and inactive states

Inactive state: integrin heads turned close to cell surface

Cell signaling extends heads to matrix

Migrating cells: focal adhesions form at the leading edge

cell matrix junctions hemidesmosomes
Cell-Matrix Junctions: Hemidesmosomes

Hemidesmosomesanchor epithelial cells to the basal lamina

α6β4 integrinsbind to lamins

long cytoplasmic tail of β subunit binds to intermediate filaments via

Plectin and BP230 and BP180 (similar to transmembrane collagens)

cell cell interactions
Cell-Cell interactions

Interactions between cells are critical for development and function of multicellular organisms

Cell-cell interactions:

Transient: activation of immune cells; migration to injury site

Stable: role in the organization of tissues.

Cell-Cell junctions allow rapid communication between cells

During embryo development, cells from one tissue specifically adhere to cells of the same tissue rather than cells of a different tissue

cell cell interactions1
Cell-Cell interactions

Cell-cell adhesion- mediated by four groups of cell adhesion molecules

Selectins, integrins, the immunoglobulin (Ig) superfamily, and cadherins

Many adhesions are divalent cation-dependent, requiring Ca2+, Mg2+ or Mn2+


Selectins- transient interactions between leukocytes and endothelial cells

Leukocytes slow down, flattened, migrate from the circulation to sites of tissue inflammation

initial adhesion

stable adhesionsbinding of integrinsto intercellular adhesion molecules(ICAMs) on endothelial cells

cell to cell junctions
Cell to Cell Junctions

Four types of Cell-Cell connections in animal cells

Adherens Junctions


Tight Junctions

Gap Junctions

adherens junctions
Adherens Junctions

Cadherin form stable cell-cell connections involve actin filaments

Also include β-catenin, p120, and α-catenin,

β-catenin and p120 bind to cadherin and help maintain stability

β-catenin binds α-catenin that interacts with actin filament of cytoskeleton


link the intermediate filament of adjacent cells

Desmoglein and desmocollin (transmembrane cadherins) bind by heterophilic interactions across the junction

Plakoglobin and plakophilin bind to the cadherins and link to the intermediate filament binding protein, desmoplakin

tight junctions
Tight Junctions

Tight junctions provide minimal adhesive strength between the cells, usually associated with adherens junctions and desmosomes in a junctional complex

tight junctions1
Tight Junctions

Tight junctions in epithelial cell form a seal that prevents free passage of molecules and ions between cells

separate apical and basolateral domains of the plasma membrane

prevent free diffusion of lipids and membrane proteins

tight junctions2
Tight Junctions

transmembrane proteins, occludin, claudin, and junctional adhesion molecule (JAM), anchored on F-actin

Bind similar proteins on the adjacent cell

Sealing the space between cells

gap junctions
Gap Junctions

open channels through the plasma membrane

allowing ions and small molecules to diffuse freely

Proteins and nucleic acids can not pass through

heart muscle cells, passage of ions through gap junctions synchronizes the contractions of neighboring cells

allow passage of some signaling molecules, such as cAMP and Ca2+, coordinating responses of cells in tissues

gap junctions1
Gap Junctions

Gap junctions are made of transmembrane proteins in the connexinfamily

6 connexins form a cylinder with an open aqueous pore in its center, called a connexon

Connexons in the plasma membrane adjacent cells align

form open channels between the two cytoplasms

gap junctions2
Gap Junctions

Specialized gap junctions occur on specific nerve cells and form an electrical synapse

Individual connexons can be opened or closed

When open, they allow rapid passage of ions between the two nerve cells