Our research aims to elucidate how proteins recognize and interact with glycans, focusing on the impact of glycan structure, nanoscale organization, and biophysical properties within the cellular glycocalyx on biological interactions. Unlike proteins and nucleic acids, glycans pose unique challenges for study due to their non-templated, post-translational nature. This characteristic has historically limited our ability to apply genetic approaches to glycan research.

To overcome this obstacle, we generate nanoscale materials that approximate the structure of native glycoconjugates but enable precise control over glycan valency and spatial organization. We've integrated these glycomimetic materials with microarray platforms, allowing us to systematically catalog their interactions with protein receptors of interest. Perhaps most excitingly, our glycomimetics can be introduced directly into the plasma membrane of cells, enabling the construction of a de novo glycocalyx with specific biological functions.

This capability allows us to manipulate and study the glycocalyx, offering new avenues for investigating how it's nanoscale organization and biophysical properties affect cellular interactions and signaling processes. By combining these approaches, we are advancing our understanding of glycan-mediated biological interactions and shedding light on the complex roles of the glycocalyx in cellular function and disease processes.

Selected Publications:

Synthetic glycoscapes: addressing the structural and functional complexity of the glycocalyx

Purcell, S. C. et. al. J. Royal Soc. Interface Focus. 2019, 9(2):20180080.

Nanoscale materials for probing the biological functions of the glycocalyx

Huang, M. L. et. al. Glycobiology. 2016, 26, 797-803.

Glycomaterials for probing host–pathogen interactions and the immune response

Huang, M. L. et. al. Exp. Biol. and Med. 2016, 241,1042-1053.

Our lab develops synthetic mucin analogs and mucosal barrier models to study glycan-mediated interactions between pathogens and host cells. Using defined glycopolymers mimicking mucin glycoproteins, we model key features of the epithelial glycocalyx and the mucosal barrier. We use this approach to study how the mucinous glycocalyx affects pathogen adhesion and infection, mainly focusing on viral and bacterial interactions. 

We investigate how the crowded nature of the glycocalyx influences protein-glycan interactions, showing, for instance, that viruses can exploit this environment to enhance binding to cell surface receptors. These findings provide new insights into how mucins may limit pathogen adhesion through biophysical means and how pathogens overcome these barriers, potentially leading to new infection prevention and treatment strategies.

Selected Publications:                                                                                        

Cell surface photoengineering enables modeling of glycocalyx shedding dynamic                                                                                    

Purcell, S. C. et. al. Chemical Science. 2022, 13 (22), 6626-6635.

Mucin-mimetic glycan arrays integrating machine learning for analyzing receptor pattern recognition by influenza A viruses
Lucas, T. M. et. al. Chem. 2021, 7 (12), 3393-3411.

Glycocalyx crowding with mucin mimetics strengthens binding of soluble and virus-associated lectins to host cell glycan receptors
Honigfort, D. J. et. al. Proc. Natl. Acad. Sci. U.S.A. 2021, 118 (40), e2107896118.

The glycocalyx, particularly its glycosaminoglycan (GAG) components, is crucial for transmitting biochemical signals from the extracellular environment to cells. GAGs, which are highly sulfated polysaccharides, recruit and present growth factors, triggering intracellular signaling and gene transcription that guide stem cell fate. We are designing materials that replicate GAG functions to activate or silence specific growth factor signaling pathways in stem cells, guiding their differentiation. This approach has potential applications in regenerative therapies, offering new possibilities for treating various diseases and injuries by manipulating how stem cells sense and respond to biochemical cues in their microenvironment.

Selected Publications:                                                                         

Glycocalyx engineering with heparan sulfate mimetics attenuates Wnt activity during adipogenesis to promote glucose uptake and metabolism

Trieger, G. W. et. al. Journal of Biological Chemistry. 2023, 299 (5), 104611.

Stem cell microarrays for assessing growth factor signaling in engineered glycan microenvironments

Michalak, A. L. et. al.  Advanced Healthcare Materials. 2022, 11 (4), 2101232.

Biologically derived neoproteoglycans for profiling protein–glycosaminoglycan interactions                                             

Porell, R. N. et. al. ACS Chemical Biology. 2022, 17 (6), 1534-1542.

Spatially controlled glycocalyx engineering for growth factor patterning in embryoid bodies

Naticchia, M. R. et. al. Biomater Sci. 2021, 9, 1652-1659.

Glycocalyx scaffolding with synthetic nanoscale glycomaterials

Huang, M. L. et. al. Biomater. Sci. 2017, 5, 1537-1540.

Glycocalyx remodeling with proteoglycan mimetics promotes neural specification in embryonic stem cells

Huang, M. L. et. al. J. Am. Chem. Soc. 2014, 136, 10565-10568. [Highlighted in the Chemical and Engineering News]