Exploiting differential surface display of chondroitin sulfate variants for directing neuronal outgrowth.
Chondroitin sulfate (CS) proteoglycans (CSPGs) are known to be primary inhibitors of neuronal regeneration at scar sites. However, a variety of CSPGs are also involved in neuronal growth and guidance during other physiological stages. Sulfation patterns of CS chains influence their interactions with various growth factors in the central nervous system (CNS), thus influencing neuronal growth, inhibition, and pathfinding. This report demonstrates the use of differentially sulfated CS chains for neuronal navigation. Surface-immobilized patterns of CS glycosaminoglycan chains were used to determine neuronal preference toward specific sulfations of five CS variants: CS-A, CS-B (dermatan sulfate), CS-C, CS-D, and CS-E. Neurons preferred CS-A, CS-B, and CS-E and avoided CS-C containing lanes. In addition, significant alignment of neurites was observed using underlying lanes containing CS-A, CS-B, and CS-E chains. To utilize differential preference of neurons toward the CS variants, a binary combinations of CS chains were created by backfilling a neuro-preferred CS variant between the microcontact printed lanes of CS-C stripes, which are avoided by neurons. The neuronal outgrowth results demonstrate for the first time that a combination of sulfation variants of CS chains without any protein component of CSPG is sufficient for directing neuronal outgrowth. Biomaterials with surface immobilized GAG chains could find numerous applications as bridging devices for tackling CNS injuries where directional growth of neurons is critical for recovery.
Department of Bioengineering, ‡Department of Medicinal Chemistry, and §Interdepartmental Program in Neuroscience, University of Utah , Salt Lake City, Utah 84112, United States.
Vimal P
VP
Swarup
Tony W
TW
Hsiao
Jianxing
J
Zhang
Glenn D
GD
Prestwich
Balagurunathan
B
Kuberan
Vladimir
V
Hlady
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D013499:Surface Properties
D002809:Chondroitin Sulfates