185:, derived from collagen binding proteins, or antibodies raised against collagens. Unfortunately, these compounds cannot target denatured collagens which are unstructured and do not present a defined 3D epitope. In addition, antibodies that were reported to distinguish specific degraded collagen fragments can only recognize one or few collagen types. In contrast, CHPs, in principle, can bind to all types of denatured collagens.
141:
199:
22:
120:(mAbs), for example. Due to their unique targeting mechanism, CHPs have a high binding specificity towards denatured collagen chains but have almost no affinity for intact (triple helical) collagen. CHPs can broadly target collagen chains that have been denatured by thermal, chemical, mechanical, or enzymatic processes, as well as multiple collagen types (e.g.,
80:
100:, its folding kinetics, and thermal stability as small triple helical models. CMPs, CLPs, and CHPs are all very similar in terms of their amino acid sequences but only when CMPs or CLPs are heated above their melting temperatures, do they exist in the dissociated, single-stranded state and can be considered as CHPs.
719:
Boudko, Sergei; Frank, Sabine; Kammerer, Richard A.; Stetefeld, Jörg; Schulthess, Therese; Landwehr, Ruth; Lustig, Ariel; Bächinger, Hans Peter; Engel, Jürgen (March 2002). "Nucleation and propagation of the collagen triple helix in single-chain and trimerized peptides: transition from third to first
202:
A fluorescence image of a sagittal section of an 18 d.p.c. mouse embryo double stained with biotinylated-CHP (detected by AlexaFluor647-streptavidin, orange) and an anti-collagen I antibody (detected by AlexaFluor555-labeled donkey anti-rabbit IgG H&L, cyan). mx, maxilla; md, mandibular bone; bp,
62:
conformation. In the single-stranded (monomeric) status, the peptide can recognize denatured collagen strands in tissues by forming a hybridized triple helix with the collagen strands. This occurs via the triple helical chain assembly and inter-chain hydrogen bonding, in a manner similar to primers
274:
Collagen offers mechanical strength in load bearing tissues in the body such as tendons, ligaments, and bone. As forces are applied to these tissues, the collagen triple helix can be damaged and unwind, and CHPs allow for molecular level detection of mechanical damage in such connective tissues.
25:
Schematic of a CHP strand (labeled with an "X" tag) hybridizing to denatured collagen chains and forming a collagen triple helix. During disease progression, tissue development, or ageing, collagen can be extensively degraded by collagenolytic proteases, causing its triple helix to unfold at the
149:
Controlled collagen turnover is crucial for embryonic development, organ morphogenesis, as well as tissue maintenance and repair. However, changes of collagen homeostasis are associated with numerous diseases and pathological conditions. Excessive collagen degradation may be associated with
1408:
Freimark, Bruce; Clark, Derek; Pernasetti, Flavia; Nickel, Jeff; Myszka, David; Baeuerle, Patrick A.; Van Epps, Dennis (July 2007). "Targeting of humanized antibody D93 to sites of angiogenesis and tumor growth by binding to multiple epitopes on denatured collagens".
1328:
Helms, Brett A.; Reulen, Sanne W. A.; Nijhuis, Sebastiaan; Graaf-Heuvelmans, Peggy T. H. M. de; Merkx, Maarten; Meijer, E. W. (2009-08-26). "High-Affinity
Peptide-Based Collagen Targeting Using Synthetic Phage Mimics: From Phage Display to Dendrimer Display".
92:(ECM). The collagen superfamily consists of 28 different types of collagen. Although the function and hierarchical structure of these collagens may vary, they all share the defining structural feature known as the triple helix, where three left handed
1206:
Nemirovskiy, O.V.; Dufield, D.R.; Sunyer, T.; Aggarwal, P.; Welsch, D.J.; Mathews, W.R. (February 2007). "Discovery and development of a type II collagen neoepitope (TIINE) biomarker for matrix metalloproteinase activity: From in vitro to in vivo".
96:(PPII) helices assemble to form a right-handed supercoiled helical motif. Short synthetic peptides known as collagen mimetic peptides (CMPs) or collagen-like peptides (CLPs) have played a major role in elucidating the 3D structure of the collagen
763:
Bächinger, Hans Peter; Morris, Nicholas P.; Davis, Janice M. (1993-01-15). "Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen".
83:
Schematic showing relationship between the CMP and CHP. Triple helical CMPs can be heated (above a defined temperature) to dissociate into monomeric CHPs; upon cooling, CHP strands can re-assemble into a triple helix over
144:
A fluorescence image of an axial cross section of a mouse heart at day 14 post myocardial infarction, stained with
Hoechst 33342 (blue) and biotin-labeled CHP (detected with AlexaFluor647-streptavidin, red). Scale bar: 1
1372:
Liang, Hui; Li, Xiaoran; Chen, Bing; Wang, Bin; Zhao, Yannan; Zhuang, Yan; Shen, He; Zhang, Zhijun; Dai, Jianwu (July 2015). "A collagen-binding EGFR single-chain Fv antibody fragment for the targeted cancer therapy".
265:
gels. Collagen is denatured by heating in the presence of SDS prior to loading the gel. The collagen bands are visualized through CHP-collagen hybridization when the gels are stained by fluorescently-labeled CHPs.
166:. CHPs can target tissues undergoing remodelling based on their ability to bind to degraded and unfolded collagen strands through triple helix formation. As a targeting moiety, CHPs offer great potential in
858:
Xu, Jingsong; Rodriguez, Dorothy; Kim, Jenny J.; Brooks, Peter C. (October 2000). "Generation of
Monoclonal Antibodies to Cryptic Collagen Sites by Using Subtractive Immunization".
1242:
Garvican, Elaine R.; Vaughan-Thomas, Anne; Innes, John F.; Clegg, Peter D. (July 2010). "Biomarkers of cartilage turnover. Part 1: Markers of collagen degradation and synthesis".
219:, formalin-fixed paraffin embedded (FFPE) sections, as well as fresh tissues. CHP is applicable to tissue specimens from multiple species and a range of diseases, such as
1560:
1032:
Weiss, Jeffrey A.; Yu, S. Michael; Buehler, Markus J.; Reese, Shawn P.; Depalle, Baptiste; San, Boi Hoa; Qin, Zhao; Li, Yang; Zitnay, Jared L. (2017-03-22).
1983:
244:
71:. The binding does not depend on a specific sequence or epitope on collagen, enabling CHPs to target denatured collagen chains of different types.
529:
Hwang, Jeongmin; Huang, Yufeng; Burwell, Timothy J.; Peterson, Norman C.; Connor, Jane; Weiss, Stephen J.; Yu, S. Michael; Li, Yang (2017-10-24).
970:
Hwang, Jeongmin; San, Boi Hoa; Turner, Neill J.; White, Lisa J.; Faulk, Denver M.; Badylak, Stephen F.; Li, Yang; Yu, S. Michael (April 2017).
807:
Holmgren, Steven K.; Taylor, Kimberly M.; Bretscher, Lynn E.; Raines, Ronald T. (April 1998). "Code for collagen's stability deciphered".
2631:
1444:
Bennink, Lucas L.; Li, Yang; Kim, Bumjin; Shin, Ik Jae; San, Boi Hoa; Zangari, Maurizio; Yoon, Donghoon; Yu, S.Michael (November 2018).
415:
Persikov, A. V.; Ramshaw, J. A.; Kirkpatrick, A.; Brodsky, B. (2000-12-05). "Amino acid propensities for the collagen triple-helix".
1857:
704:
672:
595:
Li, Yang; Ho, Daniel; Meng, Huan; Chan, Tania R.; An, Bo; Yu, Hanry; Brodsky, Barbara; Jun, Albert S.; Michael Yu, S. (2013-01-16).
181:. Using conventional methods for directly targeting collagen, researchers have to relied on collagen binding peptides selected by
1553:
1874:
2641:
1976:
112:
in a manner that is unique from other targeting mechanisms, in that they specifically recognize a unique structural motif (
2363:
2267:
2242:
908:
Li, Y.; Foss, C. A.; Summerfield, D. D.; Doyle, J. J.; Torok, C. M.; Dietz, H. C.; Pomper, M. G.; Yu, S. M. (2012-08-27).
1485:
Converse, Matthew I.; Walther, Raymond G.; Ingram, Justin T.; Li, Yang; Yu, S. Michael; Monson, Kenneth L. (2018-02-01).
207:
Fluorophore- or biotin-labeled CHPs are used as a staining agent for detecting collagen degradation and denaturation via
2395:
2324:
2262:
2257:
203:
basisphenoid bone; bo, basioccipital bone; vc, vertebral column; rb, rib; h, hipbone; d, digital bones. Scale bar: 3 mm.
2313:
2272:
2159:
2154:
2149:
2143:
2062:
1822:
1734:
1546:
1034:"Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides"
687:
Engel, Jürgen; Bächinger, Hans Peter (2005-04-12), "Structure, Stability and
Folding of the Collagen Triple Helix",
2662:
2351:
2287:
2230:
2202:
2192:
2122:
2055:
1089:
Bennink, Lucas L.; Smith, Daniel J.; Foss, Catherine A.; Pomper, Martin G.; Li, Yang; Yu, S. Michael (2017-05-08).
2340:
2075:
2037:
1969:
68:
1913:
1805:
216:
174:
972:"Molecular assessment of collagen denaturation in decellularized tissues using a collagen hybridizing peptide"
1849:
1814:
132:). Studies also showed CHPs and their fluorophore conjugates have superior stability in contact with serum.
173:
Most methods for the evaluation of collagen denaturation in disease states are indirect, such as detecting
2409:
220:
117:
113:
26:
physiological temperature due to reduced thermal stability. X may represent a biotin or fluorescent tag.
1487:"Detection and characterization of molecular-level collagen damage in overstretched cerebral arteries"
2004:
1837:
1832:
1716:
1687:
1610:
212:
89:
1446:"Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging"
2236:
2575:
2386:
1706:
1310:
840:
208:
58:
in the Xaa and Yaa positions, which confers it a strong propensity to form the collagen's unique
363:
Wahyudi, Hendra; Reynolds, Amanda A.; Li, Yang; Owen, Shawn C.; Yu, S. Michael (October 2016).
2580:
2390:
2181:
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1905:
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1506:
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1426:
1390:
1354:
1346:
1302:
1294:
1277:
Rousseau, Jean-Charles; Delmas, Pierre D (June 2007). "Biological markers in osteoarthritis".
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151:
93:
597:"Direct Detection of Collagenous Proteins by Fluorescently Labeled Collagen Mimetic Peptides"
316:
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125:
116:) for folding and chain assembly, as opposed to specific epitopes binding that is seen for
2626:
2483:
2478:
2473:
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2031:
1729:
121:
1091:"High Serum Stability of Collagen Hybridizing Peptides and Their Fluorophore Conjugates"
140:
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324:
177:(MMP) activity or quantifying collagen peptide fragments in urine, serum, or
1936:
1862:
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1751:
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1645:
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926:
777:
546:
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953:
887:
749:
733:
638:
572:
504:
444:
398:
342:
261:
CHPs can be used for visualizing many different types of collagen bands in
1961:
910:"Targeting collagen strands by photo-triggered triple-helix hybridization"
836:
793:
655:
2399:
2378:
2015:
1879:
1724:
1588:
1290:
531:"In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides"
262:
232:
1049:
2621:
2612:
2560:
2533:
2428:
2404:
2368:
2356:
2174:
2169:
2164:
2092:
1992:
1778:
1773:
1746:
463:"Targeting and mimicking collagens via triple helical peptide assembly"
249:
109:
79:
51:
39:
1342:
612:
428:
2565:
2329:
2302:
2297:
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2217:
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2197:
2132:
2127:
2085:
2080:
2042:
1884:
1867:
1538:
1166:
696:
664:
365:"Targeting collagen for diagnostic imaging and therapeutic delivery"
136:
Denatured collagen as a biomarker for tissue remodelling and damage
42:
sequence with typically 6 to 10 repeating units of the Gly-Xaa-Yaa
2590:
2585:
2555:
2550:
2528:
2510:
2488:
2097:
1946:
820:
78:
20:
1151:"Remodelling the extracellular matrix in development and disease"
2570:
1941:
1756:
1593:
1965:
1542:
1149:
Bonnans, Caroline; Chou, Jonathan; Werb, Zena (December 2014).
170:, diagnostics, and drug delivery for a wide range of diseases.
64:
108:
Single-stranded CHPs bind to denatured collagen chains and
46:
triplet, which mimics the hallmark sequence of natural
50:. A CHP peptide usually possesses a high content of
2605:
2521:
2427:
2377:
2106:
2023:
2014:
2003:
1927:
1904:
1848:
1813:
1804:
1797:
1715:
1697:
1686:
1659:
1618:
1609:
1602:
1576:
299:Shoulders, Matthew D.; Raines, Ronald T. (2009).
659:, Springer Berlin Heidelberg, pp. 185–205,
270:Detecting mechanical damage to connective tissue
914:Proceedings of the National Academy of Sciences
1977:
1554:
691:, Springer Berlin Heidelberg, pp. 7–33,
8:
2020:
2011:
1984:
1970:
1962:
1810:
1801:
1694:
1615:
1606:
1561:
1547:
1539:
461:Li, Yang; Yu, S. Michael (December 2013).
1518:
1461:
1182:
1122:
1065:
1003:
943:
925:
628:
562:
494:
388:
332:
1331:Journal of the American Chemical Society
317:10.1146/annurev.biochem.77.032207.120833
197:
139:
284:
1144:
1142:
88:Collagen is the main component of the
1279:Nature Clinical Practice Rheumatology
1155:Nature Reviews Molecular Cell Biology
1027:
1025:
1023:
965:
963:
903:
901:
899:
897:
7:
766:American Journal of Medical Genetics
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454:
410:
408:
358:
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294:
292:
290:
288:
2632:Cartilage oligomeric matrix protein
467:Current Opinion in Chemical Biology
1463:10.1016/j.biomaterials.2018.08.039
301:"Collagen structure and stability"
14:
1858:Dense irregular connective tissue
1107:10.1021/acs.molpharmaceut.7b00009
1875:Dense regular connective tissue
243:CHPs can also be labelled with
1:
1387:10.1016/j.jconrel.2015.04.029
1375:Journal of Controlled Release
381:10.1016/j.jconrel.2016.01.007
369:Journal of Controlled Release
305:Annual Review of Biochemistry
215:applications. CHPs can stain
2396:Cartilage associated protein
1503:10.1016/j.actbio.2017.11.052
1423:10.1016/j.molimm.2007.03.027
988:10.1016/j.actbio.2017.01.079
722:Journal of Molecular Biology
32:collagen hybridizing peptide
689:Topics in Current Chemistry
657:Topics in Current Chemistry
75:Collagen, CHP, CMP, and CLP
2679:
1256:10.1016/j.tvjl.2010.04.011
479:10.1016/j.cbpa.2013.10.018
245:near-infrared fluorophores
872:10.1089/02724570050198893
16:Type of synthetic peptide
1221:10.1016/j.ab.2006.10.034
175:matrix metalloproteinase
1209:Analytical Biochemistry
1095:Molecular Pharmaceutics
927:10.1073/pnas.1209721109
778:10.1002/ajmg.1320450204
547:10.1021/acsnano.7b03150
257:Collagen identification
1244:The Veterinary Journal
734:10.1006/jmbi.2002.5439
601:Bioconjugate Chemistry
217:frozen tissue sections
204:
146:
85:
27:
2410:Procollagen peptidase
1038:Nature Communications
253:fluorescent imaging.
221:myocardial infarction
201:
143:
118:monoclonal antibodies
114:collagen triple helix
82:
24:
1411:Molecular Immunology
1291:10.1038/ncprheum0508
213:immunohistochemistry
90:extracellular matrix
1337:(33): 11683–11685.
1050:10.1038/ncomms14913
920:(37): 14767–14772.
423:(48): 14960–14967.
94:polyproline II-type
2576:Matrix gla protein
2387:Prolyl hydroxylase
1491:Acta Biomaterialia
976:Acta Biomaterialia
209:immunofluorescence
205:
147:
86:
63:binding to melted
28:
2663:Peptide sequences
2650:
2649:
2601:
2600:
2423:
2422:
2391:Lysyl hydroxylase
2182:basement membrane
1959:
1958:
1955:
1954:
1900:
1899:
1793:
1792:
1789:
1788:
1682:
1681:
1570:Connective tissue
1417:(15): 3741–3750.
1343:10.1021/ja902285m
815:(6677): 666–667.
720:order kinetics".
613:10.1021/bc3005842
541:(10): 9825–9835.
429:10.1021/bi001560d
152:cancer metastasis
104:Binding mechanism
38:) is a synthetic
2670:
2021:
2012:
1986:
1979:
1972:
1963:
1811:
1802:
1730:Reticular fibers
1699:Ground substance
1695:
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1607:
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1239:
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1203:
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1137:
1136:
1126:
1101:(6): 1906–1915.
1086:
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1029:
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1007:
967:
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957:
947:
929:
905:
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2646:
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2517:
2419:
2373:
2256:transmembrane:
2102:
2006:
1999:
1990:
1960:
1951:
1923:
1896:
1844:
1785:
1725:Collagen fibers
1711:
1689:
1678:
1661:Wandering cells
1655:
1598:
1572:
1567:
1537:
1536:
1484:
1483:
1479:
1443:
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1407:
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1275:
1271:
1241:
1240:
1236:
1205:
1204:
1200:
1167:10.1038/nrm3904
1161:(12): 786–801.
1148:
1147:
1140:
1088:
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1083:
1031:
1030:
1021:
969:
968:
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697:10.1007/b103818
686:
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681:
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665:10.1007/b103823
654:
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528:
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239:In vivo imaging
196:
194:Tissue staining
191:
138:
106:
77:
67:strands during
17:
12:
11:
5:
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2059:
2047:
2046:
2045:
2040:
2027:
2025:
2024:Fibril forming
2018:
2009:
2005:Extracellular
2001:
2000:
1997:scleroproteins
1991:
1989:
1988:
1981:
1974:
1966:
1957:
1956:
1953:
1952:
1950:
1949:
1944:
1939:
1933:
1931:
1925:
1924:
1922:
1921:
1916:
1910:
1908:
1902:
1901:
1898:
1897:
1895:
1894:
1893:
1892:
1887:
1882:
1872:
1871:
1870:
1865:
1854:
1852:
1846:
1845:
1843:
1842:
1841:
1840:
1835:
1825:
1819:
1817:
1808:
1799:
1795:
1794:
1791:
1790:
1787:
1786:
1784:
1783:
1782:
1781:
1776:
1771:
1770:
1769:
1764:
1754:
1749:
1742:Elastic fibers
1739:
1738:
1737:
1727:
1721:
1719:
1713:
1712:
1710:
1709:
1703:
1701:
1692:
1688:Extracellular
1684:
1683:
1680:
1679:
1677:
1676:
1671:
1665:
1663:
1657:
1656:
1654:
1653:
1648:
1643:
1638:
1636:Reticular cell
1633:
1628:
1622:
1620:
1613:
1604:
1600:
1599:
1597:
1596:
1591:
1586:
1580:
1578:
1574:
1573:
1568:
1566:
1565:
1558:
1551:
1543:
1535:
1534:
1477:
1436:
1400:
1364:
1320:
1285:(6): 346–356.
1269:
1234:
1198:
1138:
1081:
1019:
959:
893:
866:(5): 375–385.
850:
799:
772:(2): 152–162.
755:
728:(3): 459–470.
711:
705:
679:
673:
644:
578:
510:
473:(6): 968–975.
450:
404:
348:
283:
282:
280:
277:
271:
268:
258:
255:
240:
237:
195:
192:
190:
187:
179:synovial fluid
168:histopathology
137:
134:
105:
102:
76:
73:
56:hydroxyproline
15:
13:
10:
9:
6:
4:
3:
2:
2675:
2664:
2661:
2660:
2658:
2643:
2640:
2637:
2636:
2633:
2630:
2628:
2625:
2623:
2620:
2618:
2614:
2611:
2610:
2608:
2604:
2592:
2589:
2587:
2584:
2583:
2582:
2579:
2577:
2574:
2572:
2569:
2567:
2564:
2562:
2559:
2557:
2554:
2552:
2549:
2547:
2544:
2540:
2537:
2536:
2535:
2532:
2530:
2527:
2526:
2524:
2520:
2512:
2509:
2507:
2504:
2502:
2499:
2498:
2497:
2494:
2490:
2487:
2485:
2482:
2480:
2477:
2475:
2472:
2471:
2470:
2467:
2463:
2460:
2458:
2455:
2453:
2450:
2448:
2445:
2443:
2440:
2439:
2438:
2435:
2434:
2432:
2430:
2426:
2416:
2415:Lysyl oxidase
2413:
2411:
2408:
2406:
2403:
2401:
2397:
2394:
2392:
2388:
2385:
2384:
2382:
2380:
2376:
2370:
2367:
2365:
2362:
2358:
2355:
2353:
2350:
2349:
2348:
2345:
2342:
2338:
2335:
2331:
2328:
2326:
2323:
2322:
2321:
2318:
2315:
2311:
2308:
2304:
2301:
2299:
2296:
2294:
2291:
2289:
2286:
2285:
2284:
2283:
2278:
2277:
2274:
2271:
2269:
2266:
2264:
2261:
2259:
2255:
2254:
2249:
2246:
2244:
2241:
2240:
2239:
2238:
2234:
2232:
2228:
2225:
2224:
2219:
2216:
2214:
2211:
2209:
2206:
2204:
2201:
2199:
2196:
2194:
2191:
2190:
2189:
2188:
2183:
2180:
2179:
2176:
2173:
2171:
2168:
2166:
2163:
2161:
2158:
2156:
2153:
2151:
2148:
2145:
2141:
2138:
2134:
2131:
2129:
2126:
2124:
2121:
2120:
2119:
2115:
2112:
2111:
2109:
2105:
2099:
2096:
2094:
2091:
2087:
2084:
2082:
2079:
2077:
2074:
2073:
2072:
2071:
2067:
2065:
2064:
2060:
2057:
2053:
2052:
2048:
2044:
2041:
2039:
2036:
2035:
2034:
2033:
2029:
2028:
2026:
2022:
2019:
2017:
2013:
2010:
2008:
2002:
1998:
1994:
1987:
1982:
1980:
1975:
1973:
1968:
1967:
1964:
1948:
1945:
1943:
1940:
1938:
1935:
1934:
1932:
1930:
1926:
1920:
1917:
1915:
1912:
1911:
1909:
1907:
1903:
1891:
1888:
1886:
1883:
1881:
1878:
1877:
1876:
1873:
1869:
1866:
1864:
1861:
1860:
1859:
1856:
1855:
1853:
1851:
1847:
1839:
1836:
1834:
1831:
1830:
1829:
1826:
1824:
1821:
1820:
1818:
1816:
1812:
1809:
1807:
1803:
1800:
1796:
1780:
1777:
1775:
1772:
1768:
1765:
1763:
1760:
1759:
1758:
1755:
1753:
1750:
1748:
1745:
1744:
1743:
1740:
1736:
1733:
1732:
1731:
1728:
1726:
1723:
1722:
1720:
1718:
1714:
1708:
1705:
1704:
1702:
1700:
1696:
1693:
1691:
1685:
1675:
1672:
1670:
1667:
1666:
1664:
1662:
1658:
1652:
1649:
1647:
1644:
1642:
1639:
1637:
1634:
1632:
1629:
1627:
1624:
1623:
1621:
1617:
1614:
1612:
1608:
1605:
1601:
1595:
1592:
1590:
1587:
1585:
1582:
1581:
1579:
1575:
1571:
1564:
1559:
1557:
1552:
1550:
1545:
1544:
1541:
1530:
1526:
1521:
1516:
1512:
1508:
1504:
1500:
1496:
1492:
1488:
1481:
1478:
1473:
1469:
1464:
1459:
1455:
1451:
1447:
1440:
1437:
1432:
1428:
1424:
1420:
1416:
1412:
1404:
1401:
1396:
1392:
1388:
1384:
1380:
1376:
1368:
1365:
1360:
1356:
1352:
1348:
1344:
1340:
1336:
1332:
1324:
1321:
1316:
1312:
1308:
1304:
1300:
1296:
1292:
1288:
1284:
1280:
1273:
1270:
1265:
1261:
1257:
1253:
1249:
1245:
1238:
1235:
1230:
1226:
1222:
1218:
1215:(1): 93–101.
1214:
1210:
1202:
1199:
1194:
1190:
1185:
1180:
1176:
1172:
1168:
1164:
1160:
1156:
1152:
1145:
1143:
1139:
1134:
1130:
1125:
1120:
1116:
1112:
1108:
1104:
1100:
1096:
1092:
1085:
1082:
1077:
1073:
1068:
1063:
1059:
1055:
1051:
1047:
1043:
1039:
1035:
1028:
1026:
1024:
1020:
1015:
1011:
1006:
1001:
997:
993:
989:
985:
981:
977:
973:
966:
964:
960:
955:
951:
946:
941:
937:
933:
928:
923:
919:
915:
911:
904:
902:
900:
898:
894:
889:
885:
881:
877:
873:
869:
865:
861:
854:
851:
846:
842:
838:
834:
830:
826:
822:
821:10.1038/33573
818:
814:
810:
803:
800:
795:
791:
787:
783:
779:
775:
771:
767:
759:
756:
751:
747:
743:
739:
735:
731:
727:
723:
715:
712:
708:
706:9783540232728
702:
698:
694:
690:
683:
680:
676:
674:9783540232728
670:
666:
662:
658:
651:
649:
645:
640:
636:
631:
626:
622:
618:
614:
610:
606:
602:
598:
591:
589:
587:
585:
583:
579:
574:
570:
565:
560:
556:
552:
548:
544:
540:
536:
532:
525:
523:
521:
519:
517:
515:
511:
506:
502:
497:
492:
488:
484:
480:
476:
472:
468:
464:
457:
455:
451:
446:
442:
438:
434:
430:
426:
422:
418:
411:
409:
405:
400:
396:
391:
386:
382:
378:
374:
370:
366:
359:
357:
355:
353:
349:
344:
340:
335:
330:
326:
322:
318:
314:
310:
306:
302:
295:
293:
291:
289:
285:
278:
276:
269:
267:
264:
256:
254:
252:
251:
246:
238:
236:
234:
230:
226:
222:
218:
214:
210:
200:
193:
188:
186:
184:
183:phage display
180:
176:
171:
169:
165:
161:
157:
153:
142:
135:
133:
131:
127:
123:
119:
115:
111:
103:
101:
99:
95:
91:
81:
74:
72:
70:
66:
61:
57:
53:
49:
45:
41:
37:
33:
23:
19:
2539:Tropoelastin
2495:
2468:
2436:
2346:
2336:
2319:
2309:
2280:
2235:
2185:
2139:
2117:
2068:
2061:
2049:
2030:
1707:Tissue fluid
1494:
1490:
1480:
1453:
1450:Biomaterials
1449:
1439:
1414:
1410:
1403:
1378:
1374:
1367:
1334:
1330:
1323:
1282:
1278:
1272:
1250:(1): 36–42.
1247:
1243:
1237:
1212:
1208:
1201:
1158:
1154:
1098:
1094:
1084:
1041:
1037:
979:
975:
917:
913:
863:
859:
853:
812:
808:
802:
769:
765:
758:
725:
721:
714:
688:
682:
656:
604:
600:
538:
534:
470:
466:
420:
417:Biochemistry
416:
372:
368:
308:
304:
273:
260:
248:
242:
206:
189:Applications
172:
164:osteoporosis
148:
107:
98:triple helix
87:
60:triple helix
35:
31:
29:
18:
2617:Cytokeratin
2546:Vitronectin
2227:multiplexin
1929:Specialized
1919:Mesenchymal
1890:Aponeurosis
1641:Tendon cell
1603:Composition
1584:Soft tissue
1497:: 307–318.
1381:: 101–109.
982:: 268–278.
607:(1): 9–16.
375:: 323–331.
311:: 929–958.
156:skin ageing
2248:Endostatin
2237:type XVIII
1674:Macrophage
1651:Melanocyte
1626:Fibroblast
1577:Physiology
279:References
44:amino acid
2627:Reticulin
2320:type VIII
1937:Cartilage
1906:Embryonic
1863:Submucosa
1823:Reticular
1752:Fibrillin
1669:Mast cell
1646:Adipocyte
1631:Fibrocyte
1511:1742-7061
1456:: 67–76.
1351:0002-7863
1299:1745-8382
1175:1471-0072
1115:1543-8384
1058:2041-1723
1044:: 14913.
996:1742-7061
936:0027-8424
880:0272-457X
860:Hybridoma
829:0028-0836
786:0148-7299
742:0022-2836
621:1043-1802
555:1936-0851
487:1879-0402
437:0006-2960
325:1545-4509
229:nephritis
225:arthritis
160:arthritis
48:collagens
2657:Category
2642:diseases
2638:See also
2581:Tectorin
2400:Leprecan
2310:type VII
2140:type XII
2063:type III
2016:Collagen
1880:Ligament
1619:Resident
1594:Scarring
1589:Fibrosis
1529:29225149
1472:30149231
1431:17507095
1395:25916496
1359:19642697
1315:13168927
1307:17538566
1264:20488735
1229:17187753
1193:25415508
1133:28445649
1076:28327610
1014:28161576
954:22927373
888:11128027
750:11922677
639:23253177
573:28877431
535:ACS Nano
505:24210894
445:11101312
399:26773768
343:19344236
263:SDS-PAGE
233:fibrosis
2622:Gelatin
2613:Keratin
2561:Decorin
2534:Elastin
2429:Laminin
2405:ADAMTS2
2379:Enzymes
2369:COL28A1
2364:COL27A1
2357:COL11A2
2352:COL11A1
2347:type XI
2341:COL10A1
2282:type VI
2279:other:
2273:COL25A1
2268:COL23A1
2263:COL17A1
2258:COL13A1
2243:COL18A1
2231:COL15A1
2187:type IV
2175:COL22A1
2170:COL21A1
2165:COL20A1
2160:COL19A1
2155:COL16A1
2150:COL14A1
2144:COL12A1
2118:type IX
2098:COL26A1
2093:COL24A1
2051:type II
1993:Protein
1828:Adipose
1779:Elaunin
1774:EMILIN1
1747:Elastin
1520:5794621
1184:4316204
1124:8063002
1067:5364439
1005:5462463
945:3443117
845:4425523
837:9565027
794:8456797
630:3586774
564:5656977
496:3863647
390:4936964
334:2846778
250:in vivo
110:gelatin
52:proline
40:peptide
2566:FAM20C
2337:type X
2330:COL8A2
2325:COL8A1
2314:COL7A1
2303:COL6A5
2298:COL6A3
2293:COL6A2
2288:COL6A1
2218:COL4A6
2213:COL4A5
2208:COL4A4
2203:COL4A3
2198:COL4A2
2193:COL4A1
2133:COL9A3
2128:COL9A2
2123:COL9A1
2086:COL5A3
2081:COL5A2
2076:COL5A1
2070:type V
2056:COL2A1
2043:COL1A2
2038:COL1A1
2032:type I
2007:matrix
1914:Mucoid
1885:Tendon
1868:Dermis
1806:Proper
1735:COL3A1
1717:Fibers
1690:matrix
1527:
1517:
1509:
1470:
1429:
1393:
1357:
1349:
1313:
1305:
1297:
1262:
1227:
1191:
1181:
1173:
1131:
1121:
1113:
1074:
1064:
1056:
1012:
1002:
994:
952:
942:
934:
886:
878:
843:
835:
827:
809:Nature
792:
784:
748:
740:
703:
671:
637:
627:
619:
571:
561:
553:
503:
493:
485:
443:
435:
397:
387:
341:
331:
323:
231:, and
162:, and
2606:Other
2591:TECTB
2586:TECTA
2556:FREM2
2551:FRAS1
2529:ALCAM
2522:Other
2511:LAMC3
2506:LAMC2
2501:LAMC1
2496:gamma
2489:LAMB4
2484:LAMB3
2479:LAMB2
2474:LAMB1
2462:LAMA5
2457:LAMA4
2452:LAMA3
2447:LAMA2
2442:LAMA1
2437:alpha
2114:FACIT
2107:Other
1947:Blood
1850:Dense
1838:White
1833:Brown
1815:Loose
1798:Types
1611:Cells
1311:S2CID
841:S2CID
122:Col I
84:time.
2571:ECM1
2469:beta
1942:Bone
1767:FBN3
1762:FBN2
1757:FBN1
1525:PMID
1507:ISSN
1468:PMID
1427:PMID
1391:PMID
1355:PMID
1347:ISSN
1303:PMID
1295:ISSN
1260:PMID
1225:PMID
1189:PMID
1171:ISSN
1129:PMID
1111:ISSN
1072:PMID
1054:ISSN
1010:PMID
992:ISSN
950:PMID
932:ISSN
884:PMID
876:ISSN
833:PMID
825:ISSN
790:PMID
782:ISSN
746:PMID
738:ISSN
701:ISBN
669:ISBN
635:PMID
617:ISSN
569:PMID
551:ISSN
501:PMID
483:ISSN
441:PMID
433:ISSN
395:PMID
339:PMID
321:ISSN
247:for
211:and
54:and
1515:PMC
1499:doi
1458:doi
1454:183
1419:doi
1383:doi
1379:209
1339:doi
1335:131
1287:doi
1252:doi
1248:185
1217:doi
1213:361
1179:PMC
1163:doi
1119:PMC
1103:doi
1062:PMC
1046:doi
1000:PMC
984:doi
940:PMC
922:doi
918:109
868:doi
817:doi
813:392
774:doi
730:doi
726:317
693:doi
661:doi
625:PMC
609:doi
559:PMC
543:doi
491:PMC
475:doi
425:doi
385:PMC
377:doi
373:240
329:PMC
313:doi
145:mm.
69:PCR
65:DNA
36:CHP
2659::
2229::
2184::
2116::
1995::
1523:.
1513:.
1505:.
1495:67
1493:.
1489:.
1466:.
1452:.
1448:.
1425:.
1415:44
1413:.
1389:.
1377:.
1353:.
1345:.
1333:.
1309:.
1301:.
1293:.
1281:.
1258:.
1246:.
1223:.
1211:.
1187:.
1177:.
1169:.
1159:15
1157:.
1153:.
1141:^
1127:.
1117:.
1109:.
1099:14
1097:.
1093:.
1070:.
1060:.
1052:.
1040:.
1036:.
1022:^
1008:.
998:.
990:.
980:53
978:.
974:.
962:^
948:.
938:.
930:.
916:.
912:.
896:^
882:.
874:.
864:19
862:.
839:.
831:.
823:.
811:.
788:.
780:.
770:45
768:.
744:.
736:.
724:.
699:,
667:,
647:^
633:.
623:.
615:.
605:24
603:.
599:.
581:^
567:.
557:.
549:.
539:11
537:.
533:.
513:^
499:.
489:.
481:.
471:17
469:.
465:.
453:^
439:.
431:.
421:39
419:.
407:^
393:.
383:.
371:.
367:.
351:^
337:.
327:.
319:.
309:78
307:.
303:.
287:^
235:.
227:,
223:,
158:,
154:,
130:IV
128:,
126:II
124:,
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