Extracellular Matrix 1

From CellBiology

Extracellular Matrix

Skin
Cell Adhesion
Collagen (type I) Fibres
Collagen triple helix

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  
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

  1. onto each project discussion page (Note you should add anonymously to the discussion page)
  2. your own individual student page for my assessment.

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

  1. The key points relating to the topic that your group allocated are clearly described.
  2. The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  3. Content is correctly cited and referenced.
  4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
  5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  6. Relates the topic and content of the Wiki entry to learning aims of cell biology.
  7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
  8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
  10. Develops and edits the wiki entries in accordance with the above guidelines.

Archive

MH - note that content listed below will not match exactly current lecture structure but has been selected as having similar content

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

  • Support for cells
  • Pattern of ECM regulates
    • polarity
    • cell division
    • adhesion
    • motility
  • Development
    • migration
    • differentiation
    • growth factors
Evolution of metazoan extracellular matrix PMID22431747.jpg

Evolution of metazoan extracellular matrix


ECM Features

  • stable and able to be reorganised?
  • different for different tissues

| Figure 19-61. How the extracellular matrix could, in principle, propagate order from cell to cell within a tissue

Cell Walls/ECM?
  • Cell Wall - Cells of bacteria, fungi, algae, and higher plants are surrounded by rigid cell walls (form part of the cell).
    • Gram-negative bacteria - peptidoglycan, linear polysaccharide chains crosslinked by short peptides
    • Fungi, algae, and higher plants - polysaccharides (sugar polymer), algae and higher plants mainly cellulose.
  • ExtraCellular Matrix (ECM) - animal cells of animal in tissues associated with extracellular matrix (ECM)
    • composed of secreted proteins and polysaccharides (sugar polymer)

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 Fiber structure and size

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

Collagen Type I
  • 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

MBoC Type IX collagen

Collagen Type Functions

Skin
  • 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  
Collagen type
Genes
Organization in tissue (where known) References
I
COL1A1
Fibrils in tendon, bone, skin, cornea and blood vessel walls Chu et al., 1982
COL1A2
Myers et al., 1981
II
COL2A1
Fibrils in cartilage Miller and Matukas, 1969
III
COL3A1
Forms heterotypic fibrils with type I collagen Cameron et al., 2002
IV
COL4A1
Network in basement membrane Timpl and Brown, 1996; Timpl et al., 1981
COL4A2
COL4A3
COL4A4
COL4A5
COL4A6
V
COL5A1
Forms heterotypic fibrils with type I Birk, 2001
COL5A2
COL5A3
VI
COL6A1
Fine microfibrils with ubiquitous distribution (distinct from fibrillin- Kielty et al., 1992
COL6A2
containing microfibrils
COL6A3
VII
COL7A1
Forms anchoring fibrils in skin at the dermal/epidermal junction Keene et al., 1987
(basement membrane)
VIII
COL8A1
3D hexagonal lattice in Descemet's membrane in the eye Kapoor et al., 1986; Kapoor et al., 1988;
COL8A2
Stephan et al., 2004
IX
COL9A1
Associated with type II collagen fibrils Olsen, 1997; Shimokomaki et al., 1990
COL9A2
X
COL10A1
Mat-like structure/hexagonal lattice in the hypertrophic zone of the growth plate Kwan et al., 1991
XI
COL11A1
Forms heterotypic fibrils with type II Mendler et al., 1989
COL11A2
COL2A1
XII
COL12A1
Associated with type I fibrils Keene et al., 1991; Nishiyama et al., 1994;
Zhang et al., 2003
XIII
COL13A1
Transmembrane and possibly involved in cell adhesion Latvanlehto et al., 2003
XIV
COL14A1
Associated with type I fibrils Young et al., 2000b; Young et al., 2002
XV
COL15A1
Specialized basement membranes, cleaved to produce antiangiogenic Myers et al., 1996; Ramchandran et al.,
fragment (restin) 1999
XVI
COL16A1
Component of specialized fibrillin-rich microfibrils in skin and type II Kassner et al., 2003
collagen fibrils in cartilage
XVII
COL17A1
Transmembrane component of hemidesmosomes (cell-cell junctions), which Hopkinson et al., 1998
attach epidermis to basement membrane in skin
XVIII
COL18A1
Cleaved to produce antiangiogenic fragment (endostatin) Sasaki et al., 1998
XIX
COL19A1
Radially distributed aggregates formed by association at one end in vitro Myers et al., 2003
XX
COL20A1
May be associated with type I collagen fibrils Koch et al., 2001
XXI
COL21A1
May be fibril associated, widespread expression pattern Fitzgerald and Bateman, 2001
XXII
COL22A1
Located in specific tissue junctions and may be associated with microfbrils Koch et al., 2004
XXIII
COL23A1
Transmembrane collagen identified in cell culture Banyard et al., 2003
XXIV
COL24A1
Expressed in tissues containing type I collagen Koch et al., 2003
XXV
COL25A1
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

Fibrillar collagen
  • Endoplasmic Reticulum
    • mRNA attached to ER
    • protein synthesized into ER lumen
    • cotranslational and post-translational modifications
    • endoplasmic reticulum (ER) requires Hsp47 (a molecular chaperone) transiently binds to procollagen in the ER, dissociates in the cis-Golgi or ER-Golgi intermediate compartment) PMID 27838364
    • 3 proto-a-chains form soluble procollagen
    • moved to golgi apparatus
  • Golgi Apparatus
    • packed into secretion vesicles
    • fuse with membrane
  • Outside Cell
    • procollagen processed by enzymes outside cell (ADAMTS (N-proteinase) and tolloid (C-proteinase) family enzymes)
    • assemble into collagen fibers
    • collagen fibrils form lateral Interactions of triple helices


Link: MBoC - The intracellular and extracellular events in the formation of a collagen fibril | MCB - Collagen synthesis

Collagen synthesis


Collagen fibril assembly

Collagen Assembly

YouTube Link

  • 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

Elastic Fibers Skin

MBoC - Collagen and 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

Fibrilin-microfibrils.jpg

  • 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

elastic fiber synthesis
  • 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
elastic fiber assemby model


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

Adam Byron, Margaret C Frame Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts. Curr. Opin. Cell Biol.: 2016, 39;93-100 PubMed 26930633

Lauren E Tracy, Raquel A Minasian, E J Caterson Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound. Adv Wound Care (New Rochelle): 2016, 5(3);119-136 PubMed 26989578

Kristen M Kwan Coming into focus: the role of extracellular matrix in vertebrate optic cup morphogenesis. Dev. Dyn.: 2014, 243(10);1242-8 PubMed 25044784


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

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

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

Reviews

Jessica M Bowen, Glenda J Sobey, Nigel P Burrows, Marina Colombi, Mark E Lavallee, Fransiska Malfait, Clair A Francomano Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med Genet: 2017, 175(1);27-39 PubMed 28192633

Ki M Mak, Rena Mei Basement Membrane Type IV Collagen and Laminin: An Overview of their Biology and Value as Fibrosis Biomarkers of Liver Disease. Anat Rec (Hoboken): 2017; PubMed 28187500

Shinya Ito, Kazuhiro Nagata Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone. Semin. Cell Dev. Biol.: 2016; PubMed 27838364

Elizabeth G Canty, Karl E Kadler Procollagen trafficking, processing and fibrillogenesis. J. Cell. Sci.: 2005, 118(Pt 7);1341-53 PubMed 15788652

Elizabeth D Hay The extracellular matrix in development and regeneration. An interview with Elizabeth D. Hay. Int. J. Dev. Biol.: 2004, 48(8-9);687-94 PubMed 15558460

E D Hay Extracellular matrix. J. Cell Biol.: 1981, 91(3 Pt 2);205s-223s PubMed 6172429

L B Sandberg, N T Soskel, J G Leslie Elastin structure, biosynthesis, and relation to disease states. N. Engl. J. Med.: 1981, 304(10);566-79 PubMed 7005671

Jessica E Wagenseil, Robert P Mecham New insights into elastic fiber assembly. Birth Defects Res. C Embryo Today: 2007, 81(4);229-40 PubMed 18228265


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.

PMID: 7005671

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

Moodle

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