Advisor:
Julia Babensee, Department of Biomedical Engineering, GT

Committtee: 
Andres Garcia, PhD, School of Mechanical Engineering, GT
Thomas Barker, PhD, School of Biomedical Engineering, GT
Richard Cummings, PhD, Department of Biochemistry, Emory University
Daniel Ratner, PhD, Department of Bioengineering, University of Washington
John Kauh, MD, Department of Hematology and Medical Oncology, Emory University

Dendritic cells are hypothesized to be key mediators in the immune response to implanted materials and ligation of their glycan receptors (C-type lectin Receptors (CLRs)) has been shown to have diverse effects on DC phenotype ranging from tolerogenic to pro-inflammatory.  Thus, designing future biomaterials and combination products that harness the potential of CLR ligation on DCs has great promise. However, optimal factors for DC phenotype modulation by surface presented glycans are unknown.  Additionally, studies relating DC response to glycan structures from soluble and phagocytosable displays to that of non-phagocytosable display have not been performed. 

The purpose of this study was to 1) determine the optimal molecular contextual variables of glycoconjugate presentation from a non-phagocytosable surface for modulating DC phenotype; and 2) determine if modality of glycoconjugate presentation, i.e. soluble, phagocytosable, or non-phagocytosable will modulate DC phenotype differentially. Primary human DCs were exposed to a variety of engineered, adsorbed, glycoconjugates and their subsequent phenotype assessed via a novel, in-house developed, high throughput assay.  A multivariate model was then used to determine optimal factors for glycan presentation from non-phagocytosable surfaces.  To determine the effect of the modality of glycoconjugate display on DCs, optimized glycoconjugates from 1) were adsorbed to the wells of a 384 flat well plate, delivered at varying soluble concentrations, or adsorbed to phagocytosable 1 µm beads for DC treatment. 

High isoelectric point and density glycoconjugates presented from non-phagocytosable displays modulated DC phenotype toward a pro-inflammatory phenotype to the greatest extent.  Additionally, DC response to glycoconjugates was found to be significantly different for each modality of glycan display.  This work indicates that different mechanisms are involved in DC response to glycoconjugate display modality.  These results provide indications for the future design of glycan microarray systems, biomaterials and combination products.