Extracellular Matrix Assembly in Diatoms (Bacillariophyceae)'
Extracellular Matrix (ECM)homepage.ntu.edu.tw/~mchuang/ECM.pdf · 2018-05-16 · 28 The shaping of...
Transcript of Extracellular Matrix (ECM)homepage.ntu.edu.tw/~mchuang/ECM.pdf · 2018-05-16 · 28 The shaping of...
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Connective tissue
Structural and metabolic support for other tissues
ECM
Cells
Mesoderm origin
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Extracellular matrix (ECM)
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ECM
• Ground substance
• Fibers
• Structural glycoproteins
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Ground substance
• Physical property:
– an amorphous transparent material, a semi-fluid gel
• Function:
– medium for passage of molecules and exchange of metabolites
• Chemical property:
– a mixture of long, unbranched glycosaminoglycans (GAGs) with negative charge
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Ground substance: Glycosaminoglycan (GAG)(unbranched polysaccharide chains composed of repeating
disaccharide units)
• Hyaluronic acid
– The predominant GAG in the loose supporting tissues
– without sulfate side group
GAGs that form proteoglycans:
• Chondroitin sulfate
• Dermantan sulfate
• Heparan sulfate
• Heparin
• Keratan sulfate
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Dermatan sulfate
Hyaluronan
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Highly charged side groups render
them extremely hydrophilic ---
attracting large volume of water and
positive ions (Na+): extracellular
fluid
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The linkage between a GAG chain and its core protein
(Heparan and chondroitin sulfate chains in proteoglycans)
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Pentasaccharide GAG sequence that regulates the activity of
antithrombin III
Heparin
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Keratan sulfate
• KSI: Asn
• KSII: Ser/Thr
• KSIII: KS-Man-O-Ser/Thr
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An aggrecan aggregates from fetal bovine cartilage
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What is proteoglycan?
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The relative dimensions and
volumes occupied by various
macromolecules
• Not flexible
• A huge volume for relatively small mass
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Electron micrograph of proteoglycans in the
extracellular matrix of rat cartilage
(reinfornce ground substance)
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The fibers of supporting tissue
• Collagen (including reticulin)
– Tensile strength
• Elastin
– Stretching and recoil
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Collagen
• Type I collagen:
– fibril, fibrous supporting tissue (bone, skin…)
• Type II collagen:
– fibril, hyaline cartilage
• Type III collagen: reticulin
– fibril, branched reticular supporting tissue (lymphoid
organs)
• Type IV collagen:
– mesh-like network, basement membrane
• Type VII collagen:
– anchoring fibril, beneath stratified squamous epithelia
28 types of collagen
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Some Types of Collagen and Their Properties
Type Molecular Formula
Polymerized
Form Tissue Distribution
FIBRIL-FORMING
(FIBRILLAR)
I [a 1(I)]2a2(I) fibril bone, skin, tendon,
ligaments, cornea,
internal organs
(accounts for 90% of
body collagen)
II [a 1(II)]3 fibril cartilage, intervertebral disc,
notochord, vitreous
humor of the eye
III [a 1(III)]3 fibril skin, blood vessels, internal
organs
V [a 1(V)]2a2(V) fibril (with type I) as for type I
XI a1(XI) a2(XI) a3(XI) fibril (with type II) as for type II
FIBRIL-ASSOCIATED IX a1(IX) a2(IX) a3(IX) with
type II fibrils
lateral association cartilage
XII [a 1(XII)]3 with some type I
fibrils
lateral association tendon, ligaments, some
other tissues
NETWORK-FORMING IV [a 1(IV)2a2(IV) sheetlike network basal laminae
VII [a 1(VII)]3 anchoring fibrils beneath stratified squamous
epithelia
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Electron micrograph of fibroblasts surrounded by collagen
fibrils in the connective tissue of embryonic chick skin.
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The structure of a typical collagen molecule
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Hydroxylysine and
hydroxyproline residues
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The intracellular and extracellular events involved
in the formation of a collagen fibril
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The covalent intramolecular and intermolecular cross-links formed
between modified lysine side chains within a collagen fibril.
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How type IV collagen molecules are
thought to assemble into a
multilayered network
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Type IX collagen
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The shaping of the extracellular
matrix by cells
This micrograph shows a region between two pieces of embryonic chick heart
(rich in fibroblasts as well as heart muscle cells) that has grown in culture on a
collagen gel for four days. A dense tract of aligned collagen fibers has formed
between the explants, presumably as a result of the fibroblasts in the explants
tugging on the collagen. (From D. Stopak and A.K. Harris, Dev. Biol. 90:383-
398, 1982.)
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Elastin
• Streching and elastic recoil: skin, lung, blood
vessels
• Produced by fibroblasts
• Polymerize in the ECM
• Require microfibrils of structural
glycoprotein fibrillin
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Marfan's syndrome: mutations in the
fibrillin gene
1在骨骼系統方面:體型特別高瘦,手腳及手指特別長(俗稱蜘蛛指),胸廓異常(俗稱雞胸或漏斗胸)。2眼睛系統方面:早期有深度近視、眼內水晶體脫垂、甚至造成視網膜剝離而雙眼失明。3心臟系統方面:早期易有心臟的二尖瓣脈脫垂、主動脈根部纖維壞死造成瘤樣擴大,有發生剝離的危險。
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Structural glycoproteins
• Fibril-forming molecules
– Fibrillin
– Fibronectin
• Non-filamentous proteins
– Laminin
– Entactin
– Tenascin
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Scanning electron micrograph of a basal lamina
in the cornea of a chick embryo
Basement membrane
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Basement membrane consists of
three layers• Lamina lucida
• Lamina densa
• Lamina fibroreticularis– Type III collagen (reticulin)
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Three ways in which basal laminae
(yellow lines) are organized
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Basement membrane
― mainly synthesized by the cells resting on it
• GAG: perlecan (heparan sulfate)
• Fibrous protein: type IV collagen
• Structural proteins: laminin, entactin
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Basement membrane proteins
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Cancer invasion through BM
Scanning electron micrograph of two human fibrosarcoma cells,
having digested the BD Matrigel Matrix occluding the membrane
and migrating through the 8 µm of the PET membrane.
HT-1080 Cells
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The structure of laminin
>12 isoforms: 5α, 3β, 3γ
>20 receptors
laminin-5 : α3β1, α6β4 integrins
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20 isoforms from alternative splicing of a single gene
dimer
α5β1 integrin
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Integrins: ECM receptors
Cell, Vol. 110, 673–687, September 20, 2002
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Inside-out and outside-in signals
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https://www.mechanobio.info/
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Common integrins and ECM ligands bound
Journal of Cell Science 115, 3729-3738 © 2002
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Integrin binding sites on various BM molecules
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Effects of MMPs on angiogenesis
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