title: Lipopeptides incorporated into supported phospholipid monolayers have high specific activity at low incorporation levels.
abstract: The ability to present cell adhesion molecule (CAM) ligands in controlled amounts on a culture surface would greatly facilitate the control of cell growth and differentiation. Supported lipid monolayer/bilayer systems have previously been developed that allow for presentation of CAM ligands for cell interaction; however, these systems have employed peptide loadings much higher than those used in poly(ethylene glycol) (PEG)-based immobilization systems. We report the development of synthetic methods that can be used for the efficient and versatile creation of many linear and cyclic lipid-linked peptide moieties. Using RGD-based peptides for the alpha5beta1 integrin as a model system, we have demonstrated that these lipopeptides support efficient cell binding and spreading at CAM ligand loadings as low as 0.1 mol %, which is well below that previously reported for supported lipid systems. Engineered lipopeptide-based surfaces offer unique presentation options not possible with other immobilization systems, and the high activity at low loadings we have shown here may be extremely useful in presenting multiple CAM ligands for studying cell growth, differentiation, and signaling.
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Tor W
authors.initials: TW
authors.lastname: Jensen
authors.forename: Bi-Huang
authors.initials: BH
authors.lastname: Hu
authors.forename: Shara M
authors.initials: SM
authors.lastname: Delatore
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Garcia
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Messersmith
authors.forename: William M
authors.initials: WM
authors.lastname: Miller
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides; D008074:Lipoproteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D015815:Cell Adhesion Molecules; D039081:Integrin alpha5beta1; D008024:Ligands; D055666:Lipopeptides; D008074:Lipoproteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010743:Phospholipids; C431346:RGD-lipopeptide