2015 Group 3 Project

From CellBiology

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Elastic Fibers

--Mark Hill (talk) 10:51, 16 April 2015 (EST) Only a single picture and a list of sub-headings. Please update this project page before the next practical class.


Elastin is a structural protein of elastic fibres present within the extracellular matrix of connective tissues providing strength and rigidity to stabilise the structure of cells. It provides resilience and the elastic properties of tissues and organs to repetitively deform and reform to its original shape without compromising structural integrity of cells. [1] The study of elastin was significantly hindered due to it’s insolubility. However with the discovery of tropoelastin, the soluble precursor of elastin, scientists were able to describe chemical properties of elastin. The impairment or loss of elastic tissues result in profound pathological implications.

Cross section of arteries with elastin (Left) and with elastin removed (Right)



The organisation of elastic fibres varies in different tissues. In the lungs skin and ligaments, elastic fibres are organised in a rope-like manner, in blood vessels it is organised as thin concentric sheets and has a large honeycomb structure in elastic cartilage. [1] Under a light microscope, elastin is typically recognised by its wavy appearance.

Elastic fibres are composed of two significant components; an amorphous core of highly cross-linked elastin protein that makes up 90% of elastic fibres and a fibrillar mantle of micro fibrils in the remaining 10%.Elastin is a very insoluble complex structure, being one of the most insoluble proteins of the human body. [2][1] Desmosines are a unique feature of elastin and is responsible for the it’s hydrophobic properties due to desmosines, unique feature of extensive cross-linking of fourlysine residues. [1] Tropoelastin and elastin are made significantly of only four hydrophobic amino acids: glycine, alanine, valine and proline. An important feature of composition of pure elastin is the absence of methionine, histidine and tryptophan. The microfibril region is composed of many distinct proteins.[1] It contains two types of acidic glycoprotein fibrillins organised in 8-16nm beaded fibrils with associated glycoproteins MAGP-1 and MAGP-2. Lysyl oxidase, the enzyme that initiates cross-linking within elastin and elastin binding proteins (EBP) are both found within the elastic fibre. Other microfibrillar-associated proteins include proteoglycans, osteopontin, emilin and fibulin-1.[2] [1]

Components Of Elastic Fiber

The formation of Elastic fibers is a complex process which is comprised of multiple interactions between different proteins, enyzmes and binding sites. Elastic fibers are mostly comprised of Elastin and Micro-fibrils [3] which consist make up most of the structure, the processes of formation are closely regulated and carried out by the smaller protein components; Tropoelastin, Lysyl Oxidases (LOX), Fibrilin-4 / Fibrilin-5 and Integrins


Microfibril Associated Glycoproteins


Elastin Microfibril Interface Located Protein


Lysyl Oxidase(LOX)

Lysyl Oxidase is a copper-dependant enzyme which initiates covalent cross-linking of elastin precursors from lysine residues in both collagen and elastin precursors. Lysyl oxidases are highly reactive and undergoes chemical reactions with other LOX enzymes resulting in cross-linking of elastin [4]

Assembly of Elastic Fiber

Role of MFAP-4 in Elastic fiber assembly

1) Tropoelastin is transported to the assembly sites located on a plasma membrane where it organises into small aggregates which are cross linked by Lysyl oxidases (LOX)

2) Cell surface receptors and binding proteins (e.g. Heparan Sulfate Proteoglycans) assist with the initial assembly steps. Size of the aggregating Tropoelastin is regulated by the interaction with Fibulin-4 or Fibulin-5 which also facilitates cross linking of molecules

3) Newly secreted Elastin is added to increase the size of aggregates on the cell surface

4) Aggregates of Tropoelastin are transferred to extracellular micro fibrils, new and pre-existing, which interact with the cell via integrin. Fibulin-4 or Fibulin-5 (micro-fibril association protein) assists in the transfer of the elastin aggregates into the micro fibril.

5) Elastin aggregate coalesces on the micro fibril into larger structures, this process is sometimes facilitated by Fibulin-4 / Fibulin-5

6) Newly transferred Elastin aggregates are cross-linked to one another by LOX to form the complete elastic fiber


Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves [5]

Elastin is commonly found in the arteries due to the high pressure of blood coming from the heart, and its function to supply oxygenated blood to all organs, its elasticity is important due to enormous pressure it needs to withstand. Pulmonary arterial hypertension (PAH) causes stiffness in these arteries affecting the ability for these arteries to stretch and maintain a relatively constant pressure with high blood flow. This article looks at the structure and function of this relationship in PAH and the mechanobiological adaptations that are undergone by elastic arteries in response to PAH.

Comparison between human fetal and adult skin [6]

Elastin is important in adults for restoring backing the normal tissue architecture example pinching of skin. According to this research, extracellular components such as elastin are important in the scarless healing process that takes places in on early fetal gestation. The role that elastin or another name, tropoelastin is investigated. Elastin is not found in fetal skin up till week 22. Although it is not a primary extracellular component for scarless healing in fetal wounds, it is still plays a role in skin regeneration. A comparison between fetal skin and adult skin is looked at.

Spatial Distribution and Mechanical Function of Elastin in Resistance Arteries A Role in Bearing Longitudinal Stress [7]

Arteries within the human consists of three layers and are most evident closest to the heart due to the properties that make them withhold the enormous pressure the heart pumps. The walls of the arteries exist in three layers where the outermost layer, called the tunica adventitia providing tensile strength, the hypothesis this research grouped investigated was whether the elastin fibres are subject to longitudinal stretch.

Tropoelastin - a versatile, bioactive assembly module [8]

The monomer for elastin is tropoelastin. Thus when many Tropoelastin molecules are bonded together (covalent bonds )with cross links such as lysal oxidase [9] they bind together to form the protein elastin. There is only one gene for that codes for tropoelastin and thus only one protein. The research stems on the facts that tropoelastin is compatible with synthetic and natural co-polymers. As a result of this, it enables these researches to expand upon the applications of its potential use in next-generation tailored bioactive materials such as when responding to injury. This is because large quantities of the monomer have only become accessible recently. Isolation of tropoelastin was previously intricate and inefficient due to its rate of cross linking incorporated into growing the elastic fiber in the living. However by synthesizing the elastin gene, this has allowed for a recombinant tropoelastin that is identical to the naturally secreted human form giving that compatibility that allows scientist and research to work with in a versatile way.

Insights into the role of elastin in vocal fold health and disease [10]

Elastin can be defined as a an extracellular matrix protein that is responsible for tissue elastic recoil. Therefore, because of its function it can then be assumed that it is found in different parts of the human body that require tissue recoiling. For example, lungs(30%)- expansion when inhaling and exhaling air, large arteries (70%)-to be able to recoil back to their shape consistently as blood is bumped through them, skin (2-4%)- to be able to withstand stretches and sustain its original shape. Elastin can also be found in the vocal fold of the lamina propria, making up 9% of the total protein. Thus, the lamina propria experiences greater amounts of mechanical strain relative to skin but less when compared to lungs and arteries.

Damaged Elastic Lamina in Blood Vessel.png

Clinical Significance

Interaction between Ebola virus and the extracellular matrix [11]

Ebola virus is an aggressive pathogen that causes a highly lethal hemorrhagic fever syndrome in humans with mortality rates varying between 50 to 90%. Based on previous studies, it was suggested that the Ebola virus glycoprotein is the main determinant of vascular cell injury and thus it was proposed that the direct Ebola virus replication-induced structural damage of endothelial cells triggers the hemorrhagic diathesis. This study suggested, by using the ISM technique (information spectrum method), that the EMILINs (Elastin Microfibril Interface Located Proteins) play an important role in interaction between Ebola virus and the endothelial extracellular matrix, contributing to the infection and the pathogenesis of Ebola virus by damage of the extracellular matrix and vascular homeostasis.

Matrix metalloproteinases in destructive lung disease [12]

The lung is a very complex and sophisticated matrix structure on which lung epithelium and endothelium reside. This study aimed to review the roles matrix metalloproteinases play in the development of pulmonary enphysema, a destructive process encountered mostly in smokers and a disease component of chronic obstructive pulmonary disease (COPD). Matrix metalloproteinases contribute substantially to lung matrix degradation during the evolution of cigarette smoke induced emphysema by destruction of both elastin and collagen matrix proteins.

EMILIN2 regulates platelet activation, thrombus formation and clot retraction [12]

The EMILIN proteins are a family of extracellular matrix glycoproteins that play important role not only in elastogenesis and vascular architecture, but also in hemostasis and thrombosis. EMILIN2, Elastin Microfibril Interface Protein2, was identified as a gene expressed during cardiovascular development, on cardiac stem cells, and in heart tissue in animal models of heart disease. In humans, EMILIN2 gene is located on the short arm of chromosome 18, and patients with partial and complete deletion of this chromosome region have cardiac malformations. The results presented by this study indicated that EMILIN2 is necessary for platelet aggregation, clot retraction and thrombus formation, showing that it has multiple influences in pathophysiology of thrombosis and suggested that its role as a prothrombotic risk factor may arise from its effects on platelet aggregation.

Vitamin A deficiency and alterations in the extracellular matrix [13]

Vitamin A or retinol can be considered the most multifunctional vitamin in mammals. It has a lot of biological roles and it is known to modulate the synthesis of extracellular matrix proteins, including elastin. For this reason, the structure and composition of this extracellular compartment is deeply altered as a result of vitamin A deficiency. Its deficiency, along with protein malnutrition, is currently the most common and serious nutritional disorder worldwide. This review aimed to show that altered extracellular matrix will potentially compromise organ function and lead to diseases, like liver, pulmonary and renal fibrosis, which are common pathological states associated with alterations in the extracellular matrix.


  1. 1.0 1.1 1.2 1.3 1.4 1.5 <pubmed>9851686</pubmed>
  2. 2.0 2.1 <pubmed>12082143</pubmed>
  3. <pubmed>18228265</pubmed>
  4. <pubmed>19813219</pubmed>
  5. <pubmed>PMC2593497</pubmed>
  6. <pubmed>PMC2799629</pubmed>
  7. <pubmed>PMC3380608</pubmed>
  8. <pubmed>PMC3879170</pubmed>
  9. <pubmed>PMC3190022</pubmed>
  10. <pubmed>PMC3190022</pubmed>
  11. <pubmed>PMC4333865</pubmed>
  12. <pubmed>PMC4319747</pubmed>
  13. <pubmed>PMC4245576</pubmed>

12.Matrix metalloproteinases in destructive lung disease. http://www.sciencedirect.com/science/article/pii/S0945053X15000396