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

Ding, Hui and Fox, Irving and Patil, Rameshwar and Galstyan, Anna and Black, Keith L. and Ljubimova, Julia Y. and Holler, Eggehard (2017) Polymalic Acid Tritryptophan Copolymer Interacts with Lipid Membrane Resulting in Membrane Solubilization. JOURNAL OF NANOMATERIALS: 4238697. ISSN 1687-4110, 1687-4129

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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/WWWfirst attaches to themembrane 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 themembrane 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.

Item Type: Article
Uncontrolled Keywords: CELL-PENETRATING PEPTIDES; BREAST-CANCER-TREATMENT; LINEAR POLYETHYLENIMINE; UNILAMELLAR VESICLES; POLY(ACRYLIC ACID); TUMOR-GROWTH; POLYMERS; DELIVERY; BILAYERS; PERMEABILIZATION;
Subjects: 500 Science > 580 Botanical sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eggehard Holler
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 12:57
Last Modified: 19 Feb 2019 15:01
URI: https://pred.uni-regensburg.de/id/eprint/29

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