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Light-Mediated Approach for Modeling Dynamic Properties of the Mucin Glycocalyx

Abstract

The cell surface glycocalyx is a dense layer of macromolecules of variant structure and size, the latter of which is an underappreciated factor in many cellular functions, such as cell/pathogen interactions, growth factor signaling, cell adhesion/migration, and signal transduction. Methods to alter cellular glycocalyx composition would allow for the study and control of these functions. In the absence of genetic tools to manipulate glycosylation with high spatial specificity, chemical and materials-based approaches offer unique opportunities. In this study, we developed a transient model for glycocalyx remodeling by photopatterning cells with a novel mucin-mimicking, photocleavable lactose glycopolymer. Subsequently, we applied this model to modify the lectin-binding ability of Lec8 CHO cells, mammalian cells lacking lactosyl residues. Characterization of the lactose glycopolymer, as a free molecule and attached to cells, revealed that photocleavage occurs within 2 minute of UV treatment, confirming the biological utility of this model. Incorporation of lactose glycopolymers into the plasma membrane altered native glycocalyx dynamics and increased lactose-specific lectin, Erythrina cristagalli (ECA/ECL), binding at the cell surface. Subsequent cleavage of glycopolymers following UV treatment reduced lectin binding by 80%. These results established this photocleavable glycopolymer as a dynamic model for glycocalyx remodeling and achievement of specific cellular outcomes. In the future, this model can be utilized for biomimicry of events such as mucin shedding during pathogenic invasion and cancer progression.

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