Efficient internalization of TAT peptide in zwitterionic DOPC phospholipid membrane revealed by neutron diffraction.
The aim of this study is to investigate the interactions between TAT peptides and a neutral DOPC bilayer by using neutron lamellar diffraction. The distribution of TAT peptides and the perturbation of water distribution across the DOPC bilayer were revealed. When compared to our previous study on an anionic DOPC/DOPS bilayer (X. Chen et al., Biochim Biophys Acta. 2013. 1828 (8), 1982-1988), a much deeper insertion of TAT peptides was found in the hydrophobic core of DOPC bilayer at a depth of 6.0Å from the center of the bilayer, a position close to the double bond of fatty acyl chain. We conclude that the electrostatic attractions between the positively charged TAT peptides and the negatively charged headgroups of phospholipid are not essential for the direct translocation. Furthermore, the interactions of TAT peptides with the DOPC bilayer were found to vary in a concentration-dependent manner. A limited number of peptides first associate with the phosphate moieties on the lipid headgroups by using the guanidinium ions pairing. Then the energetically favorable water defect structures are adopted to maintain the arginine residues hydrated by drawing water molecules and lipid headgroups into the bilayer core. Such bilayer deformations consequently lead to the deep intercalation of TAT peptides into the bilayer core. Once a threshold concentration of TAT peptide in the bilayer is reached, a significant rearrangement of bilayer will happen and steady-state water pores will form.
College of Biological Science and Biotechnology, Fuzhou University, 2 Xue Yuan Road, University Town, 350116 Fuzhou, Fujian, PR China.; The University of Edinburgh, Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom.
Xiaochao
X
Chen
College of Biological Science and Biotechnology, Fuzhou University, 2 Xue Yuan Road, University Town, 350116 Fuzhou, Fujian, PR China.
Shutao
S
Liu
Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, F-38042 Grenoble Cedex 9, France.
Bruno
B
Deme
Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, F-38042 Grenoble Cedex 9, France.
Viviana
V
Cristiglio
Canadian Neutron Beam Centre, National Research Council, Chalk River, ON K0J 1P0, Canada.
Drew
D
Marquardt
The University of Edinburgh, Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom.
Richard
R
Weller
College of Biological Science and Biotechnology, Fuzhou University, 2 Xue Yuan Road, University Town, 350116 Fuzhou, Fujian, PR China.
Pingfan
P
Rao
College of Biological Science and Biotechnology, Fuzhou University, 2 Xue Yuan Road, University Town, 350116 Fuzhou, Fujian, PR China.
Yunqiang
Y
Wang
The University of Edinburgh, Royal (Dick) School of Veterinary Studies, Easter Bush, Roslin, Midlothian EH25 9RG, United Kingdom. Electronic address: j.bradshaw@ed.ac.uk.
Jeremy
J
Bradshaw
D015696:Gene Products, tat / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D033363:Neutron Diffraction / Q000379:methods*; D010713:Phosphatidylcholines / Q000737:chemistry*
D015696:Gene Products, tat; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; C017251:1,2-oleoylphosphatidylcholine
TAT peptide; cell penetrating peptide; neutron diffraction; phospholipid