Title

Efficient internalization of TAT peptide in zwitterionic DOPC phospholipid membrane revealed by neutron diffraction

Document Type

Article

Publication Date

5-1-2017

Publication Title

Biochimica et Biophysica Acta - Biomembranes

Volume

1859

Issue

5

First Page

910

Keywords

cell penetrating peptide, neutron diffraction, phospholipid, TAT peptide

Last Page

916

Abstract

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 6.0 Å 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.

DOI

10.1016/j.bbamem.2017.01.036

ISSN

00052736

E-ISSN

18792642

PubMed ID

28153495

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