title: Structural investigation of PEG-fibrinogen conjugates.
abstract: Controllable bio-synthetic polymeric hydrogels made from fibrinogen-poly(ethylene glycol) adducts have been successfully employed in tissue engineering. The structural consequences of PEG conjugation to fibrinogen (i.e., PEGylation) in such a hydrogel network are not fully understood. The current investigation details the structural alterations caused to the reduced fibrinogen polypeptides by the covalent attachment of linear or branched PEG chains. The structure of PEGylated fibrinogen polypeptides were comprehensively characterized using small angle X-ray scattering, light scattering, and cryo-transmission electron microscopy. These characterizations concur that the bio-synthetic hybrids self-assemble into elongated objects, having a protein core of about 50 A in diameter decorated with multiple PEG chains. Conjugates with branched PEG chains were shorter, and have lower average molecular weight compared to conjugates with linear chains. The diameter of the protein core of both samples was similar, suggesting a tail-to-head aggregation of the PEGylated fibrinogen polypeptide. A more complete understanding of this unique structural arrangement can provide further insight into the full extent of biofunctional accessibility in a biomaterial that combines the advantages of synthetic polymers with bioactive proteins.
authors.affiliation: Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ilya
authors.initials: I
authors.lastname: Frisman
authors.forename: Ron
authors.initials: R
authors.lastname: Orbach
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.forename: Havazelet
authors.initials: H
authors.lastname: Bianco-Peled
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D020285:Cryoelectron Microscopy / Q000379:methods; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D008027:Light; D008954:Models, Biological; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D010455:Peptides; D011108:Polymers; D011092:Polyethylene Glycols; D005340:Fibrinogen
references.citation: Biophys J. 2008 Apr 1;94(7):2914-25
references.pmid: 18178662
references.citation: Biotechnol Bioeng. 2006 Dec 20;95(6):1061-9
references.pmid: 16921532
references.citation: Bioorg Med Chem. 2007 Aug 15;15(16):5396-405
references.pmid: 17561403
references.citation: Biomacromolecules. 2005 May-Jun;6(3):1226-38
references.pmid: 15877337
references.citation: J Phys Colloid Chem. 1947 Jan;51(1):18-32
references.pmid: 20286386
references.citation: Adv Drug Deliv Rev. 2002 Jun 17;54(4):459-76
references.pmid: 12052709
references.citation: Ann N Y Acad Sci. 2005 Jun;1047:386-94
references.pmid: 16093513
references.citation: Biomaterials. 2005 May;26(15):2467-77
references.pmid: 15585249
references.citation: Acta Biomater. 2007 Jan;3(1):33-41
references.pmid: 17098488
references.citation: J Biomed Mater Res A. 2007 Mar 15;80(4):874-84
references.pmid: 17072852
references.citation: Biomacromolecules. 2002 Jul-Aug;3(4):710-23
references.pmid: 12099815
references.citation: Cardiovasc Pathol. 2003 Nov-Dec;12(6):295-310
references.pmid: 14630296
references.citation: J Biotechnol. 2002 Mar;90(1):3-15
references.pmid: 12069046
references.citation: Biomaterials. 2006 Mar;27(8):1496-506
references.pmid: 16243393
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5142-7
references.pmid: 12702764
references.citation: Biomol Eng. 2007 Dec;24(6):643-9
references.pmid: 18023612
references.citation: Artif Cells Blood Substit Immobil Biotechnol. 2006;34(4):381-93
references.pmid: 16818412
references.citation: Annu Rev Biomed Eng. 2001;3:225-43
references.pmid: 11447063
references.citation: J Thromb Thrombolysis. 1998;5(1):9-14
references.pmid: 10608044
references.citation: Biomaterials. 2007 Sep;28(26):3876-86
references.pmid: 17576008
references.citation: J Biophys Biochem Cytol. 1959 Jan 25;5(1):11-6
references.pmid: 13630928
references.citation: Biophys J. 2008 Jan 1;94(1):173-81
references.pmid: 17827244