Noncovalent Cell Surface Engineering: Incorporation of Bioactive Synthetic Glycopolymers into Cellular Membranes

• Published in: Journal of the American Chemical Society 2008-05, Vol.130 (18), p.5947-5953
• Main Authors: Rabuka, David, Forstner, Martin B, Groves, Jay T, Bertozzi, Carolyn R
• Format: Article
• Language: English
• Subjects: Animals; Biomimetic Materials - chemical synthesis; Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Butanones - chemistry; Carrier Proteins - chemistry; Carrier Proteins - metabolism; CD55 Antigens - chemistry; CD55 Antigens - metabolism; Cell Membrane - chemistry; Cell Membrane - metabolism; CHO Cells; Cricetinae; Cricetulus; Folate Receptors, GPI-Anchored; Glycosylphosphatidylinositols - chemistry; Glycosylphosphatidylinositols - metabolism; Hydrophobic and Hydrophilic Interactions; Microscopy, Fluorescence; Mucins - chemical synthesis; Mucins - chemistry; Mucins - metabolism; Polymers - chemical synthesis; Polymers - chemistry; Polysaccharides - chemical synthesis; Polysaccharides - chemistry; Polysaccharides - metabolism; Protein Engineering; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja710644g

The controlled addition of structurally defined components to live cell membranes can facilitate the molecular level analysis of cell surface phenomena. Here we demonstrate that cell surfaces can be engineered to display synthetic bioactive polymers at defined densities by exogenous membrane insertion. The polymers were designed to mimic native cell-surface mucin glycoproteins, which are defined by their dense glycosylation patterns and rod-like structures. End-functionalization with a hydrophobic anchor permitted incorporation into the membranes of live cultured cells. We probed the dynamic behavior of cell-bound glycopolymers bearing various hydrophobic anchors and glycan structures using fluorescence correlation spectroscopy (FCS). Their diffusion properties mirrored those of many natural membrane-associated biomolecules. Furthermore, the membrane-bound glycopolymers were internalized into early endosomes similarly to endogenous membrane components and were capable of specific interactions with protein receptors. This system provides a platform to study cell-surface phenomena with a degree of chemical control that cannot be achieved using conventional biological tools.