title: A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes.
abstract: The multifarious Tat peptide derived from the HIV-1 virus exhibits antimicrobial activity. In this article, we use Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) to investigate the mechanisms of action of Tat (44-57) and Tat (49-57) on bacterial-mimetic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (sodium salt) (DMPG) membranes. The results reveal that both peptides disrupt DMPC/DMPG membranes via a surface-active (carpet-like) mechanism. The magnitude of this disruption is dependent on both membrane and peptide properties. Firstly, less disruption was observed on the more negatively charged membranes. Secondly, less disruption was observed for the longer and slightly more hydrophobic Tat (44-57) peptide. As a comparison, the behaviour of the two Tat peptides on mammalian-mimetic DMPC/cholesterol membranes was investigated. Consistent with the literature no membrane disruption was observed. These results suggest that both electrostatic and hydrophobic interactions, as well as peptide geometry, determine the antimicrobial activity of Tat. This should guide the development of more potent Tat antibiotics.
authors.affiliation: School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Stefania
authors.initials: S
authors.lastname: Piantavigna
authors.forename: George A
authors.initials: GA
authors.lastname: McCubbin
authors.forename: Solveig
authors.initials: S
authors.lastname: Boehnke
authors.forename: Bim
authors.initials: B
authors.lastname: Graham
authors.forename: Leone
authors.initials: L
authors.lastname: Spiccia
authors.forename: Lisandra L
authors.initials: LL
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000378:metabolism; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism*; D008322:Mammals; D008563:Membrane Lipids / Q000378:metabolism*; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism
chemical_list: D015696:Gene Products, tat; D008563:Membrane Lipids; D010743:Phospholipids; D002784:Cholesterol