Int J Curr Pharm Res, Vol 9, Issue 3, 24-26Review Article



Dept. of Pharmaceutics, St James College of Pharmaceutical Sciences, Chalakudy, Kerala, St James Hospital Trust Pharmaceutical Research Centre (DSIR Recognized), Chalakudy, Kerala

Received: 28 Dec 2016, Revised and Accepted: 27 Mar 2017


Collagen is the sole protein found predominantly in the animal kingdom. The main source of collagen which had been land animals previously is being replaced by other alternative sources due to certain health related, religious and social concerns. Thus additional reliable, safer and productive options for collagen extraction have been studied extensively since then. Its wide-ranging application, especially in the biomedical and cosmetic field, is also a basis for its study to have become a topic of interest among the researchers. Isolation of collagen from the processing wastes of marine organisms has been receiving a lot of attention recently due to the promising outcome it brings forth. In the current review, we have focused upon squid, mainly its processing waste, as an alternative source of collagen including the studies carried out on the same to a certain extent.

Keywords: Type I collagen, Fish collagen, Squid, etc


Collagen is the primary and most profuse structural protein found in the animal kingdom, comprising nearly 25-30% of the whole-body protein content. It is typically found in fibrous tissues such as skin, ligaments, tendons, skin, corneas, cartilage, bones, blood vessels, teeth, etc. It exists predominantly in the form of a network like structure or as extracellular fibrils. Collagen has a unique ability to form insoluble fibers known as fibrils possessing high tensile strength [1]. Depending upon the degree of mineralization, collagen tissues may be classified as rigid (bone), complaint (tendon) or a gradient from rigid to the complaint (cartilage). Each collagen containing tissue fulfills its specific function as a result of the variation in the physical and chemical characteristics, composition of its amino acid, polypeptide chain, etc. It is involved in a variety of biological functions [2]. It also plays an indispensible role in cellular processes such as its motion, proliferation, apoptosis, etc [3]. Collagen exhibits exceptional biocompatibility, safety, biodegradability, cell-adhesive properties, low immunogenicity, etc [4, 5].

Structure and chemistry

Collagen is 300 mm long with a diameter of 1.5 to 2 nm and axial ratio of 150. The collagen protein (ie the mature collagen is also known as tropocollagen) exists in the form of a triple helix consisting of three polypeptide chains (alpha chains) in its 3-D form. These 3 chains may be either identical as in type II and III, known as homotrimer or may have two or more different chains as in type I, IV and V known as heterotrimer. Each of these polypeptide chains are coiled in the form of a left-handed helix and all the three winds up together form a right-handed helix. The polypeptide chain has nearly 1000 amino acid residues (with a molecular weight of nearly 100kDa) in it with a pattern of Gly-X-Y in it, where the X and Y positions are occupied by the imino acids, proline and hydroxyproline. Considering the helix structure, glycine is centrally located whereas the Pro and Hyp are arranged along its outer side [6]. The glycine content in most fish species is nearly 30-33% and about 16-18% of proline and hydroxyproline [7]. The Pro and Hyp are mainly responsible for the stabilization of the triple helix through hydrogen bond by the promoting polyproline II conformation [8]. It limits the rotation of the polypeptide chains involved and thus renders stability to its structure. The interchain hydrogen bonds are responsible for the stabilisation of the three polypeptide chains. The non-helical telopeptide zone at the terminal region of the molecule is usually involved in inter and intramolecular covalent cross-link of the alpha chain. At this region, the helical behaviour of the molecule is lost due to the presence of globular proteins which are involved in the crossliking. The hydrogen bond formed between the glycine residues amino group and the carbonyl group of other chains residues also contributes for the stabilization of the collagen triple helix [9]. Extracting the collagen with acid solution helps in obtaining the same with its alpha-helical configuration intact.

Types of collagen

There are nearly 28 different types of collagen classified based on the chain difference in their molecule [10]. The common types are type I-V. Some of them form network-like structures (Type IV, VIII, X, etc) whereas the others for a fiber-like structure. Different types of collagen are found in different sites of the body such as type I in bones and tendons, type II in cartilage, type III in skin, type IV in basement membrane, etc. [11] Among the various types present, type I collagen is considered the most important as it is present in almost all sites of the body and is the most abundant one. Type I collagen has α and β chains in the ratio of 2:1.

Applications of collagen

Collagen provides various health benefits such as

  • Acts as a digestive aid.
  • Exhibits anti-aging property.
  • Contributes in weight loss.
  • Makes the joints and bones healthy.
  • Helps improve athletic performance by an increase in muscle mass.
  • Improves sleep quality.
  • Strengthens hair, nail and teeth.

Collagen is widely used in the food, pharmaceutical, medical, biomedical and cosmeceutical fields, leather and film industries, etc. It is widely used as a biomaterial in the biomedical field. Additional uses, especially in the food industry, include the production of gelatin, sausage casings, nutritional supplements, etc. In the cosmeceutical field, it is available in different forms as an anti-ageing product. Since collagen can be made available in varied forms such as sponges, tubes, powders, sheets, dispersion, injectable solution, etc; it is applicable in tissue engineering, ophthalmology, wound dressing, burn treatments, etc [12, 13].

Sources of collagen

Collagen has been extracted mainly from the connective tissues of various sources such as animal as well marine source. Till recently, the animal source had been used commercially for collagen extraction, especially the porcine and bovine skin and bones. But it was due to the onset of diseases such as Bovine spongiform encephalopathy (BSE), Transmissible spongiform encephalopathy (TSE), Foot-and-mouth disease (FMD), etc and also cultural and social concerns, other alternative and safer sources of collagen were probed for [14]. Since then serious studies have been carried out on collagen extraction from marine vertebrates and invertebrates such as fishes, starfish, sponges, octopus, squid, sea urchin, cuttlefish, sea anemone, jellyfish, prawn, etc [15-18].

Collagen content varies among different species. The properties of collagen extracted from different sources, be it animal or marine source, greatly depends on its habitat, species, targeted tissue and body temperature of the organism used, etc. [19, 20].

Marine processing wastes which are a threat to the environment can be utilized effectively for the extraction of many value added products which also includes collagen. Fish wastes such as skin, bones, fins, scales are being studied extensively.

The processing wastes of squid includes its skin, head, viscera, backbones or pens, ink, tentacles, fins, mantle, etc. It makes up 60% of its total body weight [21]. While considering the squids, its collagenous membrane which becomes detached during the mechanical processing procedure can be utilized for the same [22]. Collagen content found in the mantle of the squid constitutes nearly 10% of its total protein content. Due to the commercial importance and the presence of high protein content especially collagen in the squid, we have chosen squid for our research. Till date, squid collagen that has been studied are included in table 1.

Table 1: Squid collagen studies

Squid Scientific name Tissue Collagen Ref
Atlantic short-finned squidAtlantic long-finned squid IllexillecebrosusLoligopealei Mantle 3-11% 23
Jumbo/Giant squid Dosidicusgigas Fin, arms, mantle. 2433
Squid Todarodespacificus Skin 25
Squid Todarodespacificus Mantle muscle Type SQ-I and SQ-II 26
European squid Loligo vulgaris Mantle ASC(5.1%) and PSC(24.2% onDry weight basis 27
Persian Gulf squid Uroteuthisduvauceli Skin Type I 28
Squid Ommastrephesbartrami Skin ASC and PSC type I collagen 29
Diamondback squid Thysanoteuthis rhombus Skin ASC(1.3%) and PSC(35.6% on dry weight basis) 27.5 ̊C, 30

Squid collagen was found to have a porous structure which encourages cell adhesion, morphogenesis, aggregation and growth. Collagen concentration in the mantle of certain squid species like Loligo and Ilex were found to be from 3 to 11.1% while in Dosidicusgigas, it was up to 18.33% [31, 32]. Variation in concentration of collagen obtained is seen as a result of high rate of protein turnover occurring in the muscles of the squid. This is evident due to their fast growth requiring just one to two years to attain maturity. Much more studies are still being carried out with different species from different parts of the world.

Applications of squid collagen

The collagen extracted from the Persian Gulf Squid was shown to be suitable to be used as a substrate in three-dimensional cell culture system, which in turn could be used effectively as a tool in biomedical research. This can be made use of for the development of newer drugs and treatment protocol particularly in the case of cancer. The collagen extracted from the mantle of Jumbo squid (Dosidicusgigas) mantle collagen has potential to be used as a plasticiser agent and can be used for biofilm preparation when blended with chitosan. Jumbo squid fin and skin collagen hydrolysates exhibited antioxidant activity. The by-products of Jumbo squid, mainly its fin and arm collagen hydrolysates were shown t exhibit antioxidant, anti-mutagenic and anti-proliferative activity and it was concluded to be studied further to confirm its role as a food additive. The enzymatic hydrolysates of the collagen obtained from the skin of squid (Todarodespacificus) showed antioxidant, anti-elastase and tyrosinase inhibitory activities. The mantle of the squid Loligo vulgaris demonstrated its potential as a substituted source of collagen-derived materials.


Collagen is a protein with numerous applications in varied fields such as biomedical, pharmaceutical, cosmetic, etc. Collagen can be obtained from various sources. Out of all sources available, collagen from marine source is being focused upon lately. Considering the aquatic source, the processing wastes are being targeted as it helps to prevent environmental pollution apart from providing a safer, economic and reliable source of collagen. In the current review, we had tried to summarise the research work carried out on squid and its collagen, especially from its processing waste. The squid was found to be a promising source of collagen and further research needs to be carried out to further explore its potential.


Declare none


  1. Gelse K, Pöschl E, Aigner T. Collagens-structure, function, and biosynthesis.Adv Drug Delivery Rev 2003;55:1531–46.
  2. Voet D, Voet JG. Biochemistry. New York: John Wiley and sons; 1995.
  3. Cho SY, Klemke RL. Extracellular-regulated kinase activation and Cas/Crk coupling regulate cell migration and suppress apoptosis during the invasion of the extracellular matrix. J Cell Biol 2000;149:223–36.
  4. Lee C, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm 2001;221:1-22.
  5. Glowacki J, Mizuno S. Collagen scaffolds for tissue engineering. Biopolymers 2008;89:338–44.
  6. Yonath A, Traub W. Polymers of tripeptides as collagen models: IV. Structure analysis of poly(l-prolyl-glycyl-l-proline). J Mol Biol 1969;43:461.
  7. Gómez-Guillén MC, López-Caballero ME, Alemán A, López de Lacey A, Giménez B, Montero P. Antioxidant and antimicrobial peptide fractions from squid and tuna skin gelatin. Sea By-Products as Real Material: New Ways of Application; 2010. p. 89-115.
  8. Ledward DA. Gelation of gelatin. In: Mitchell JR, Ledward DA. ed. Functional Properties of Food Macromolecules. London: Elsevier; 1986. p. 171-201.
  9. Uriarte Montoya MH, Arias Moscoso JL, Plascencia Jatomea M, Santacruz Ortega H, Rouzaud Sández O, Cardenas Lopez JL, et al. Jumbo squid (Dosidicusgigas) mantle collagen: extraction, characterization, and potential application in the preparation of chitosan-collagen biofilms. Bioresour Technol 2010;101:4212-9.
  10. WichudaJankangram, Sunthorn Chooluck, Busarakum Pomthong. Comparison of the properties of collagen extracted from dried jellyfish and dried squid. Afr J Biotechnol 2016;15:642-8.
  11. Silvipriya KS, Krishna Kumar K, Bhat AR, Dinesh Kumar B, Anish John, Panayappanlakshmanan. Collagen: animal sources and biomedical application. J Appl Pharm Sci 2015;5:123-7.
  12. Se-Kwon Kim, Eresha Mendis. Bioactive compounds from marine processing byproducts–a review. Food Res Int 2006;39:383-93.
  13. Chi Lee H, Anuj Singla, Yugyung Lee. Biomedical applications of collagen. Int J Pharm 2001;221:1–22.
  14. Jongjareonrak A, Benjakul S, Visessanguan W, Nagai T, Tanaka M. Isolation and characterization of acid and pepsin-solubilised collagens from the skin of brown stripe red snapper (Lutjanusvitta). Food Chem 2005;93:475-84.
  15. Subramanian A, Lin HY. Crosslinked chitosan: its physical properties and the effects of matrix stiffness on chondrocyte cell morphology and proliferation. J Biomed Mater Res 2008;75A:742-53.
  16. Sugiura H, Yunoki S, Kondo E, Ikoma T, Tanaka J, Yasuda K. In vivo biological responses and bio-resorption of tilapia scale collagen as a potential biomaterial. J Biomater Sci Polymer 2009;20:1353-68.
  17. Song E, Yeon Kim, Chun T, Byun HJN, Lee YM. Collagen scaffolds derived from a marine source and their biocompatibility. Biomaterials 2006;27:2951-95.
  18. Strawich E, Nimni ME. Properties of a collagen molecule containing three identical components extracted from bovine articular cartilage. Biochemistry 1971;10:3905-11.
  19. Falguni P, Adhikari B, Dhara S. Isolation and characterization of fish scale collagen of higher thermal stability. Bioresource Technol 2010;101:3737–42.
  20. Rigby BJ. Amino acid composition and thermal stability of the skin collagen of the antarctic icefish. Nature 1968;219:166-7.
  21. Ezquerra Brauer JM, Uriarte Montoya MH, Arias Moscoso JL, PlascenciaJatomea M. By-products from jumbo squid (Dosidicusgigas): a new source of collagen bio-plasticizer? In: Luqman M. ed. Recent advances in plasticizers; 2012. p. 19–44.
  22. Yata M, Yoshida C, Fujisawa S, Mizuta S, Yoshinaka R. Identification and characterization of molecular species of collagen in the fish skin. J Food Sci 2001;66:247–51.
  23. Sikorski ZE, Kołodziejska I. The composition and properties of squid meat. Food Chem 1986;20:213-24.
  24. Torres Arreola W, Pacheco-Aguilar R, Sotelo-Mundo RR, Rouzaud Sández O, Ezquerra-Brauer JM. Partial characterization of collagen from mantle, fin, and arms of jumbo squid (Dosidicusgigas) Cienc. Tecnol Aliment 2008;6:101-8.
  25. Nam KA, You SG, Kim SM. Molecular and physical characteristics of Squid (Todarodespacificus) skin collagens and biological properties of their enzymatic hydrolysates. J Food Sci 2008;73:C249-55.
  26. Shohshi Mizuta, Reiji Yoshinaka, Mamoru Sato, Yoshiaki Itoh, Morihiko Sakaguchi. Subunit composition of two distinct types of collagen in the muscle of the squid todarode-spacificus. Fisheries Sci 1994;60:597-602.
  27. Cozza N, Bonani W, Motta A, Migliaresi C. Evaluation of alternative sources of collagen fractions from Loligo vulgaris squid mantle. Int J Biol Macromol 2016;87:504-13.
  28. Ladan Delphi, Houri Sepehri, Elaheh Motevaseli, Mohammad Reza Khorramizadeh. Collagen extracted from persian gulf squid exhibits anti-cytotoxic properties on apple pectic treated cells: assessment in an in vitro bioassay model. Iran J Public Health 2016;45:1054-63.
  29. Mingyan Yan, Bafang Li, Xue Zhao. Isolation and characterization of collagen from squid (Ommastrephesbartrami) skin. J Ocean University China 2009;8:191-6.
  30. Nagai T. Collagen from diamondback squid (Thysanoteuthis rhombus) outer skin. Z. Naturforsch 2004;59c:271-5.
  31. Ilona Kołodziejska. The composition and properties of squid meat. Food Chem 1986;20:213-24.
  32. Torres Arreola W, Pacheco Aguilar R, Sotelo Mundo RR, Rouzaud Sández O. Ezquerrabrauerjm partial characterization of collagen from mantle, fin, and arms of jumbo squid (Dosidicusgigas). Ciencia Y Tecnología Alimentaria 2008;6:101-8.
  33.  antioxidant, antimutagenic and antiproliferative activities of collagen hydrolysates of jumbo squid (Dosidicusgigas) byproducts. Food Sci Technol 2015;35:1-8.

How to cite this article

  • Dhanya P Joy, K Krishnakumar, B Dineshkumar, Silvipriya KS. Collagen from squid and its biological activity. Int J Curr Pharm Res 2017;9(3):23-25.

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Type I collagen, Fish collagen, Squid, etc



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International Journal of Current Pharmaceutical Research
Vol 9, Issue 3, 2017 Page: 24-26

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Dhanya P. Joy

K. Krishna Kumar

B. Dinesh Kumar

Silvipriya K. S.


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