Mechanisms of peptide amphiphile internalization by SJSA-1 cells in vitro.
Self-assembly of peptide amphiphiles into nanostructures makes them attractive for a variety of applications in drug and peptide delivery. We here report on the interactions of micelles composed of a palmitoylated, pro-apoptotic peptide derived from p53 tumor suppressor protein with a human cancer cell line. Characterization of self-assembly in aqueous buffered solutions revealed formation of elongated rod-like micelles above a critical micelle concentration. Our results however demonstrate that monomers instead of micelles are internalized, a finding that correlates with the dynamic nature of the assemblies and the noncovalent interactions that hold them together. Internalization is shown to occur via adsorption-mediated, energy-dependent pathways, resulting in accumulation of the material in endocytic vesicles. We conclude that palmitoylation of peptides is an efficient way to increase peptide permeability inside SJSA-1 cells and that increased micelle stability would be required for intact micelle internalization.
Missirlis
Dimitris
D
Department of Chemical Engineering and Materials, University of California, Santa Barbara, California 93106, USA. dimis@engineering.ucsb.edu
Khant
Htet
H
Tirrell
Matthew
M
D000327:Adsorption; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004705:Endocytosis; D006801:Humans; D008081:Liposomes; D008823:Micelles; D008969:Molecular Sequence Data; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000378:metabolism
D008081:Liposomes; D008823:Micelles; D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019308:Palmitic Acid; D051736:Proto-Oncogene Proteins c-mdm2