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Journal of Nanomaterials
Volume 2017 (2017), Article ID 4238697, 11 pages
https://doi.org/10.1155/2017/4238697
Research Article

Polymalic Acid Tritryptophan Copolymer Interacts with Lipid Membrane Resulting in Membrane Solubilization

1Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2Institut für Biophysik und Physikalische Biochemie der Universität Regensburg, Regensburg, Germany

Correspondence should be addressed to Hui Ding

Received 19 January 2017; Revised 27 March 2017; Accepted 16 April 2017; Published 21 May 2017

Academic Editor: Abdelwahab Omri

Copyright © 2017 Hui Ding et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Anionic polymers with membrane permeation functionalities are highly desirable for secure cytoplasmic drug delivery. We have developed tritryptophan containing copolymer (P/WWW) of polymalic acid (PMLA) that permeates membranes by a mechanism different from previously described PMLA copolymers of trileucine (P/LLL) and leucine ethyl ester (P/LOEt) that use the “barrel stave” and “carpet” mechanism, respectively. The novel mechanism leads to solubilization of membranes by forming copolymer “belts” around planar membrane “packages.” The formation of such packages is supported by results obtained from studies including size-exclusion chromatography, confocal microscopy, and fluorescence energy transfer. According to this “belt” mechanism, it is hypothesized that P/WWW first attaches to the membrane surface. Subsequently the hydrophobic tryptophan side chains translocate into the periphery and insert into the lipid bilayer thereby cutting the membrane into packages. The reaction is driven by the high affinity between the tryptophan residues and lipid side chains resulting in a stable configuration. The formation of the membrane packages requires physical agitation suggesting that the success of the translocation depends on the fluidity of the membrane. It is emphasized that the “belt” mechanism could specifically function in the recognition of abnormal cells with high membrane fluidity and in response to hyperthermia.