Biomedical Applications of Collagen Proteins

Abstract: Collagen protein is the main structural component of extracellular matrix and plays an important role in mechanical stability of various tissues, tissue structure and morphology. One-third of total proteins in human body are collagen proteins. There are 28 kinds of collagen proteins with different advanced tissue structure. The most common one can form fibre. These proteins are assembled with unique hierarchical structure. Collagen molecules are paralleled and cross-linked, forming long fiber nanostructure and more advanced structure.

Keywords: Collagen Proteins, Protein Synthesis, Collagen Types and Functions, Collagen Applications

1. Collagen Protein Structure

Collagen protein family members are trimer, consisting of 3 α chains. Each chain has the repetitive sequence (Gly-X-Y)n. X and Y are usually proline and hydroxyproline. Collagen proteins are synthesized by coded gene, and become mature protein by post-translational modification and processing. Collagen proteins forming fibre are procollagen during synthesis, and has one collagen or COL structural domain at least, as well as non-collagen or NC structural domain. Collagen molecules produced by processed procollagen assemble striped fibers. Each fibrous collagen molecule is about 300 nanometers in length and 1.5 nanometers in diameter. In the fibre, collagen molecules are interlaced from N to C, forming D cycle repetition mode.

2. Collagen Types and Functions

Collagen proteins code 45 genes at least and 28 different kinds of collagen glycoprotein in the genome of vertebrates and more advanced invertebrates. These collagen proteins are assigned to roman numerals(I-XXVIII) according to discovery time. There are four types of collagen proteins based on the structure and function, including fibrous collagens(e.g. Ⅰ, Ⅱ, Ⅲ, Ⅴ, Ⅺ, ⅩⅣ and ⅩⅩⅦ, the most common types are Ⅰ, Ⅱ and Ⅲ. ), fibril-associated collagen with interrupted triple-helices(FACIT, e.g. Ⅸ, Ⅻ, ⅩⅣ, ⅩⅥ, ⅩⅨ and ⅩⅫ, these collagens don’t form fibres, but regulate the assembly and size of fibre via the interaction with other collagens), reticular collagens(e.g. Ⅳ, Ⅶ and ⅩⅩⅧ), membrane-associated collagens with interrupted triple-helices(MACITs, e.g. ⅩⅢ, ⅩⅩⅢ and ⅩⅩⅤ, these collagens have specific structural domains which play an important role in biological function).

3. Collagen Protein Synthesis

The biosynthesis of collagen protein includes intracellular and extracellular stages. In nucleus, genetic information of collagen molecules is transcribed to ribosome by mRNA, synthesizing peptide chains containing over 1,000 amino acid residues. These peptide chains enter endoplasmic reticulum(ER) for hydroxylation and glycosylation modification. The modified dissolved collagen proteins form triple helix procollagen and are secreted to outside the cells. Then, they hydrolyze peptide chain on N and C terminal to form protocollagen. Under neutral pH conditions, attraction of charges between molecules automatically polymerize protocollagen to collagenous fiber. The polymerization is unstable and requires for the convention of lysine to allysine, depending on the catalysis of lysine oxidase. Allysine further reacts with histidine to form aldehyde histidine, and finally aldimine condensation with 5-hydroxylysine happens to form schiff base structure. Then, tension and toughness of collagen microfibrils increase. The solubility decreases and insoluble collagen fibers form.

4. Collagen For Medical Applications

Collagen proteins are widely applied in biomedicine, tissue engineering and regenerative medicine. Collagen proteins are used as scaffold materials to promote the regeneration of damaged tissue, e.g. repair of skin, cartilage, and skeletal tissue. In beauty products and skin care, collagen proteins can improve the elasticity and tightness of the skin, and decrease wrinkles and fine lines. As the carrier or package of drugs, collagen proteins can control drug release, improving bioavailability, stability, efficacy and safety of drugs. It's reported that overexpression of ECM gene is related to poor prognosis of cancer patients. The TCGA data analysis shows mutation rate of somatic cell in gastric cancer collagen gene is higher than background mutation rate. The mutation of somatic cell in COL7A1 gene can predict survival benefits. Collagen proteins may be effective targets for anti-tumor therapy. The fusion between anti-tumor cytokines(e.g. IL-2, IL-12) and collagen-binding protein lumican can extend the tumor retention time, improving the efficacy of immunotherapy.

5. Recommended Products

5.1. Recombinant Proteins

Cat.No	Product Name	MW(kDa)	Host
P1833	Recombinant Human COL1A1	34.9 kDa	E.Coli
P0719	Recombinant Human COL1A2	40.3 kDa	E.Coli
P2704	Recombinant Human COL2A1	48.0 kDa	E.Coli
P8480	Recombinant Human COL3A1	40.6 kDa	E.Coli
P1164	Recombinant Human COL6A1	33.2 kDa	E.Coli
P8139	Recombinant Human COL6A2	44.9 kDa	E.Coli
P8685	Recombinant Human COL8A1	43.2 kDa	E.Coli
P2017	Recombinant Human COL15A1	21.7 kDa	E.Coli

5.2.Antibodies

Cat.No	Product Name	MW(kDa)	Type
FNab09910	Collagen Type I antibody		pAb
FNab01836	Collagen Type I antibody	118 kDa	pAb
FNab01837	Collagen Type II antibody	141 kDa	pAb
FNab01838	Collagen Type III(N-Terminal) antibody	140-150 kDa	pAb
FNab01839	Collagen Type III antibody	140-150 kDa	pAb
FNab01844	Collagen Type IV antibody	200 kDa	pAb
FNab01846	COL6A1 antibody	140 kDa	pAb
FNab01845	COL6A2 antibody	140 kDa	pAb
FNab01847	COL8A1 antibody	73 kDa	pAb
FNab10495	COL14A1 antibody		pAb
FNab10026	COL10A1 antibody	30 kDa	pAb
FNab01848	COL16A1 antibody	158 kDa	pAb
FNab02762	COL18A1 antibody	19 kDa, 27 kDa	pAb
FNab01849	COL23A1 antibody	70 kDa	pAb

5.3. ELISA Kits

Cat.No	Product Name	Range	Sensitivity
EH7533	Human COLI ELISA Kit	0.313-20ng/ml	0.188ng/ml
EH1092	Human PINP ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH2867	Human COL4 ELISA Kit	0.781-50ng/ml	0.469ng/ml
EH0958	Human COL1A1 ELISA Kit	0.313-20ng/ml	0.188ng/ml
EH2866	Human COL3 ELISA Kit	0.625-40ng/ml	0.375ng/ml
EH1638	Human COL7A1 ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH0960	Human PIIINP ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH2865	Human COL2 ELISA Kit	46.875-3000pg/ml	28.125pg/ml
EH1093	Human ICTP ELISA Kit	78.125-5000pg/ml	46.875pg/ml
EH2867-HS	Human COL4 ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH0957	Human PICP ELISA Kit	62.5-4000pg/ml	37.5pg/ml
EH0959	Human COL2A1 ELISA Kit	0.625-40ng/ml	0.375ng/ml
EH2870	Human COL6α1 ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH0746	Human COL3A1 ELISA Kit	31.25-2000pg/ml	18.75pg/ml
EH0996	Human CTXI ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH0080	Human PIVNP ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH2143	Human PIICP ELISA Kit	31.25-2000pg/ml	18.75pg/ml
EH4851	Human PCOL-I ELISA Kit	62.5-4000pg/ml	37.5pg/ml
EH0540	Human COL15A1 ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH0725	Human COL28A1 ELISA Kit	0.156-10pmol/ml	0.094pmol/ml
EH1006	Human CTXII ELISA Kit	0.156-10ng/ml	0.094ng/ml
EH1635	Human COL9A3 ELISA Kit	31.25-2000pg/ml	18.75pg/ml
EH1637	Human COL10A1 ELISA Kit	0.313-20ng/ml	0.188ng/ml
EH2144	Human PIINP ELISA Kit	93.75-6000pg/ml	56.25pg/ml
EH2859	Human COL11α1 ELISA Kit	39.063-2500pg/ml	23.438pg/ml
EH2862	Human COL15 ELISA Kit	0.313-20ng/ml	0.188ng/ml
EH2869	Human COL6 ELISA Kit	3.125-200ng/ml	1.875ng/ml
EH4704	Human PCII ELISA Kit	0.156-10ng/ml	0.094ng/ml

REFERENCES

[1]Collagen type XIV is proportionally lower in the lung tissue of patients with IPF, PMID: 37938243.
[2]Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials, PMID: 38037709.