title: Noncovalent cell surface engineering: incorporation of bioactive synthetic glycopolymers into cellular membranes.
abstract: 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.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rabuka
authors.forename: Martin B
authors.initials: MB
authors.lastname: Forstner
authors.forename: Jay T
authors.initials: JT
authors.lastname: Groves
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002074:Butanones / Q000737:chemistry*; D018958:CD55 Antigens / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008856:Microscopy, Fluorescence; D009077:Mucins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011134:Polysaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism
chemical_list: D002074:Butanones; D018958:CD55 Antigens; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols; D009077:Mucins; D011108:Polymers; D011134:Polysaccharides; D011956:Receptors, Cell Surface; C057920:3-buten-2-one