Extracellular Matrix 1
Contents
- 1 Extracellular Matrix
Extracellular Matrix
Introduction
This lecture introduces the materials lying outside the cell, known collectively as the extracellular matrix (ECM). There is no one matrix though, with different tissues having their own specific ECM, which may be dynamic or static in structure. In particular the ECM has significant roles in normal tissue development, function and disease. This matrix is manufactured by cells, secreted and modified outside the cell by several different enzymes.
This lecture introduces the ECM, describes the major fiber (fibre) and matrix components and will then cover the major ECM glycoproteins and experimental studies of ECM function.
- Spelling - UK sulphate, US sulfate ; UK fibre, US fiber
Lecture Slides: 2017 Lecture PDF
2015 Group Projects
Take a look at the 2015 student group projects designed around ECM - 2015 Extracellular Matrix: Group 1 - Small Leucine-Rich Proteoglycans | Group 2 - Integrins | Group 3 - Elastic Fibres | Group 4 - Fibronectin | Group 5 - Laminin | Group 6 - Collagen | Group 7 - Basement Membrane
The projects Collagen and Elastic Fibres relate specifically to this lecture content.
Lab 7 Individual Assessment |
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The following peer assessment exercise should be completed before next lab (Lab 8 - 2 May) as your individual assessment for this week (lab missed due to public holiday).
Your answer should be pasted in 2 places
Each individual will provide a brief assessment of the other groups projects. This should take the form of a brief critical (balanced) assessment identifying both the positive (good) and negative (bad) aspects of the project page as it currently exists online. You may if you choose, use the final project assessment criteria as a guide. Though you are also welcome to use your own criteria. Group Assessment Criteria
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Archive
MH - note that content listed below will not match exactly current lecture structure but has been selected as having similar content
- 2016 | 2010 | 2009 | 2008 | 2008 4 slides/page |
Objectives
- Understand the localisation and origin of extracellular matrix
- Understand the 3 major components
- fibers, proteoglycans (matrix), adhesive glycoproteins
- Broad understanding of structure and function
- collagen fibers
- elastin fibers
- proteoglycans
ECM Function
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![]() Evolution of metazoan extracellular matrix |
ECM Features
- stable and able to be reorganised?
- different for different tissues
Cell Walls/ECM? |
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ECM Structure
- Glycoproteins
- Fibers
- Collagen- main fibers
- Elastin
- Hydrated Matrix
- Proteoglycans
- high carbohydrate
- Adhesive
- Laminin
- Fibronectin
Shapes and Sizes ECM molecules
- Note the relative size and differential contribution of protein (green) and glycosaminoglycan (red)
Collagen
- tensile strength and elasticity
- Tendons
- Cartilage
- Bone
- half total body proteins (by weight)
Collagen Components
- Insoluble glycoprotein
- protein + carbohydrate
Protein
- high glycine
- high proline
- hydroxylysine
- hydroxyproline
- (gly-X-Y)n - any of 20 standard amino acids may occupy the X position and/or the Y position (Y position- hydroxylysine, hydroxyproline)
- most frequently observed triplet is Gly-Pro-Hyp (10.5%) PMID 9724608
Carbohydrate
- glucose
- galactose
Collagen Structure
Collagen Protein
- 3 polypeptide (a) chains
- left hand helix, forms fibers
- many different (vertebrate) collagens by different combinations of a-chains
- Type I, II, III
- main fibers, flexible
- Type I
- bone, skin, tendons
- 90% of all collagen
- Type II
- cartilage
Collagen Fibers
- Type I, II, III cross striated
- e.g. tendons - type I fibrils, have a 67-nm period striations and are oriented longitudinally (direction of the stress)
- showing overlapping packing of individual collagen molecules
- reticular fibres type III, support individual cells
- Type IV fine unstriated
- sheet-like supportive meshwork
- mature basal laminae
- tracks for embryonic migration
- barriers for cell migration
- Type V-XII
- smaller diameter fibers than I-III
- no striations
Collagen Interactions
Collagen fibril types can interact with a variety of non-fibrous collagen types (microfiber)
- fibrous collagens—types I, II, III, and V
- Cartilage - types II (fiber) and IX collagen microfibrils
- Tendons - type I fibrils bound and linked by type VI microfibrils.
MCB - Interactions of fibrous and nonfibrous collagens
Collagen Type Functions
- Collagen Type I - skin, tendon, vascular, ligature, organs, bone (main component of bone)
- Collagen Type II - cartilage (main component of cartilage)
- Collagen Type III - reticular fibers with type I.
- Collagen Type IV - forms bases of cell basement membrane
- Collagen Type V - hair and nail
You do not need to know the protein table below in detail, just the major type/functions shown above.
Collagen Proteins
Collagen Types | |||
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Collagen type | Organization in tissue (where known) | References | |
I | Fibrils in tendon, bone, skin, cornea and blood vessel walls | Chu et al., 1982 | |
Myers et al., 1981 | |||
II | Fibrils in cartilage | Miller and Matukas, 1969 | |
III | Forms heterotypic fibrils with type I collagen | Cameron et al., 2002 | |
IV | Network in basement membrane | Timpl and Brown, 1996; Timpl et al., 1981 | |
V | Forms heterotypic fibrils with type I | Birk, 2001 | |
VI | Fine microfibrils with ubiquitous distribution (distinct from fibrillin- | Kielty et al., 1992 | |
containing microfibrils | |||
VII | Forms anchoring fibrils in skin at the dermal/epidermal junction | Keene et al., 1987 | |
(basement membrane) | |||
VIII | 3D hexagonal lattice in Descemet's membrane in the eye | Kapoor et al., 1986; Kapoor et al., 1988; | |
Stephan et al., 2004 | |||
IX | Associated with type II collagen fibrils | Olsen, 1997; Shimokomaki et al., 1990 | |
X | Mat-like structure/hexagonal lattice in the hypertrophic zone of the growth plate | Kwan et al., 1991 | |
XI | Forms heterotypic fibrils with type II | Mendler et al., 1989 | |
XII | Associated with type I fibrils | Keene et al., 1991; Nishiyama et al., 1994; | |
Zhang et al., 2003 | |||
XIII | Transmembrane and possibly involved in cell adhesion | Latvanlehto et al., 2003 | |
XIV | Associated with type I fibrils | Young et al., 2000b; Young et al., 2002 | |
XV | Specialized basement membranes, cleaved to produce antiangiogenic | Myers et al., 1996; Ramchandran et al., | |
fragment (restin) | 1999 | ||
XVI | Component of specialized fibrillin-rich microfibrils in skin and type II | Kassner et al., 2003 | |
collagen fibrils in cartilage | |||
XVII | Transmembrane component of hemidesmosomes (cell-cell junctions), which | Hopkinson et al., 1998 | |
attach epidermis to basement membrane in skin | |||
XVIII | Cleaved to produce antiangiogenic fragment (endostatin) | Sasaki et al., 1998 | |
XIX | Radially distributed aggregates formed by association at one end in vitro | Myers et al., 2003 | |
XX | May be associated with type I collagen fibrils | Koch et al., 2001 | |
XXI | May be fibril associated, widespread expression pattern | Fitzgerald and Bateman, 2001 | |
XXII | Located in specific tissue junctions and may be associated with microfbrils | Koch et al., 2004 | |
XXIII | Transmembrane collagen identified in cell culture | Banyard et al., 2003 | |
XXIV | Expressed in tissues containing type I collagen | Koch et al., 2003 | |
XXV | Transmembrane collagen, cleaved form present in Alzheimer‚ amyloid plaques in neurons | Hashimoto et al., 2002 | |
Table modified from Canty EG, Kadler KE. Procollagen trafficking, processing and fibrillogenesis. J Cell Sci. 2005 Apr 1;118(Pt 7):1341-53. Review. PMID: 15788652 | JCS Link |
Collagen Synthesis
Link: MBoC - The intracellular and extracellular events in the formation of a collagen fibril | MCB - Collagen synthesis |
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Collagen Assembly |
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- Collagen in the ECM is modified/cleaved by matrix metalloproteinases (MMPs) - family of enzymes (calcium-dependent zinc-containing endopeptidases)
Collagen Diseases
Collagen Diseases - Excess
- fibrosis
- lung- pulmonary fibrosis
- overproduction of collagen I
- liver- over consumption of alcohol
- arteries- atherosclerosis
Collagen Diseases - Insufficient
- Ehlers-Danlos syndrome
- defect in the synthesis of Type I or III collagen
- rubber-man
- skin and tendons easily stretched
- contortionists often suffer from this disease
- Osteogenesis imperfecta
- brittle-bone syndrome
- mutation in Type I procollagen
- fail to assemble triple helix
- degrade imperfect collagen
- Leads to fragile bones
- Scurvy
- dietary Vitamin C deficiency
- needed for hydroxylation
- Proline -> Hydroxyproline
- form too few hydrogen bonds in collagen
- skin, bone, teeth weakness and malformation
- blood vessels weakened, bleeding
Elastin
Elastin in Aorta PMID 18248974
- elastin and elastic fibres
- uncoils into an extended conformation when the fiber is stretched
- recoils spontaneously as soon as the stretching force is relaxed
Elastic fibers are composed of a core of cross-linked elastin embedded within a peripheral mantle of microfibrils.
Microfibrils
- may regulate assembly and organization of elastic fibers by acting as a scaffold
- guiding tropoelastin deposition
- aggregates of threadlike filaments
- periodically spaced globular domains (beads) connected by multiple linear arms
- beaded structure is parallel fibrillin monomers aligned head-to-tail
- fibulin-5 induces elastic fiber assembly and maturation by organizing tropoelastin and cross-linking enzymes onto microfibrils PMID: 17371835
Links: MBoC - Collagen and elastin
Elastin Structure
- protein Mr 64 to 66 kDa
- composed of the amino acids glycine, valine, alanine, and proline
- cross-linked tropoelastin monomers
- first secreted as soluble precursors (tropoelastin)
- assembly and crosslinking of tropoelastin monomers
- form insoluble elastin matrix into functional fibres
- lysine residues in the cross-linking domain of secreted tropoelastin rapidly cross-linked (both inter- and intra-molecularly by lysyl oxidase)
- hydrophobic segments - elastic properties
- α-helical segments (alanine- and lysine-rich) - form cross-links between adjacent molecules
Links: Nature - Fibulin-5 is an elastin-binding protein
Elastin Function
- structural integrity and function of tissues
- requiring reversible extensibility or deformability
- high levels in tissues that require elasticity
- lung, skin, major blood vessels
Elastin Disorders
References
Recent Reviews
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Textbooks
Essential Cell Biology
- Essential Cell Biology Chapter 19 p594-604
Molecular Biology of the Cell
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
- Molecular Biology of the Cell 4th ed. - V. Cells in Their Social Context Chapter 19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix
- The Extracellular Matrix of Animals
Molecular Cell Biology
Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999
- Molecular Cell Biology - Chapter 22. Integrating Cells into Tissues
- Cell-Matrix Adhesion
The Cell- A Molecular Approach
Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000
- The Cell- A Molecular Approach
- The Cell - A Molecular Approach - III. Cell Structure and Function Chapter 12. The Cell Surface
- The Extracellular Matrix
Essentials of Glycobiology, 2nd ed.
Varki, A.; Cummings, R.D.; Esko, J.D.; Freeze, H.H.; Stanley, P.; Bertozzi, C.R.; Hart, G.W.; Etzler, M.E., editors Plainview (NY): Cold Spring Harbor Laboratory Press; 2008
Search Online Textbooks
- "extracellular matrix" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
- "collagen" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
- "elastin" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
- "glycosaminoglycan" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
Books
PubMed
- PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
- PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
- Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
- Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez
Search Pubmed
- "extracellular matrix" Entrez all databases
- "collagen" Entrez all databases
- "elastin" Entrez all databases
- "glycosaminoglycan" Entrez all databases
- "proteoglycan" Entrez all databases
- note the spelling differences when carrying out other related ECM searches: UK sulphate, US sulfate ; UK fibre, US fiber
Reviews
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Articles
- Sandberg LB, Soskel NT, Leslie JG. Elastin structure, biosynthesis, and relation to disease states. N Engl J Med. 1981 Mar 5;304(10):566-79. Review.
Links
- Marfan syndrome is an autosomal dominant disorder that has been linked to the FBN1 gene on chromosome 15. FBN1 encodes a protein called fibrillin
2017 Course Content
Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2017 Revision
2017 Laboratories: Introduction to Lab | Fixation and Staining |
2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha
Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G