Lipopeptides Incorporated into Supported Phospholipid Monolayers Have High Specific Activity at Low Incorporation Levels

• Published in: Journal of the American Chemical Society 2004-11, Vol.126 (46), p.15223-15230
• Main Authors: Jensen, Tor W, Hu, Bi-Huang, Delatore, Shara M, Garcia, Ana Sofia, Messersmith, Phillip B, Miller, William M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biological membranes; Cell Adhesion; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Endothelium, Vascular - cytology; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cells - cytology; Humans; Integrin alpha5beta1 - chemistry; Integrin alpha5beta1 - metabolism; Ligands; Lipopeptides; Lipoproteins - chemical synthesis; Lipoproteins - chemistry; Lipoproteins - metabolism; Membrane physicochemistry; Molecular biophysics; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - metabolism; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - metabolism; Phospholipids - chemistry; Phospholipids - metabolism; Substrate Specificity; Surface Properties
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja048684o

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 α5β1 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.