Characterization of type I collagen gels modified by glycation.
Chronic exposure to reducing sugars due to diabetes, aging, and diet can permanently modify extracellular matrix (ECM) proteins. This non-enzymatic glycosylation, or glycation, can lead to the formation of advanced glycation end products (AGE) and crosslinking of the ECM. This study investigates the effects of glycation on the properties of type I collagen gels. Incubation with glucose-6-phopshate (G6P), a reducing sugar that exhibits similar but more rapid glycation than glucose, modified the biological and mechanical properties of collagen gels. Measures of AGE formation that correlate with increased complications in people with diabetes, including collagen autofluorescence, crosslinking, and resistance to proteolytic degradation, increased with G6P concentration. Rheology studies showed that AGE crosslinking increased the shear storage and loss moduli of type I collagen gels. Fibroblasts cultured on glycated collagen gels proliferated more rapidly than on unmodified gels, but glycated collagen decreased fibroblast invasion. These results show that incubation of type I collagen gels with G6P increases clinically relevant measures of AGE formation and that these changes altered cellular interactions. These gels could be used as in vitro models to study ECM changes that occur in diabetes and aging.
Francis-Sedlak
Megan E
ME
Pritzker Institute of Biomedical Science and Engineering, Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 6063, USA. franmeg@iit.edu
Uriel
Shiri
S
Larson
Jeffery C
JC
Greisler
Howard P
HP
Venerus
David C
DC
Brey
Eric M
EM
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005453:Fluorescence; D005782:Gels; D019298:Glucose-6-Phosphate / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D012212:Rheology; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D024042:Collagen Type I; D003432:Cross-Linking Reagents; D005782:Gels; D019298:Glucose-6-Phosphate