TY - JOUR
T1 - A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes
AU - Piantavigna, Stefania
AU - McCubbin, George
AU - Boehnke, Solveig
AU - Graham, Bimbil
AU - Spiccia, Leone
AU - Martin, Lisandra
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0005273611000666
U2 - 10.1016/j.bbamem.2011.03.002
DO - 10.1016/j.bbamem.2011.03.002
M3 - Article
SN - 0005-2736
VL - 1808
SP - 1811
EP - 1817
JO - BBA Biomembranes
JF - BBA Biomembranes
IS - 7
ER -
