A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes

Stefania Piantavigna, George McCubbin, Solveig Boehnke, Bimbil Graham, Leone Spiccia, Lisandra Martin

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36 Citations (Scopus)


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. (C) 2011 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1811 - 1817
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number7
Publication statusPublished - 2011

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