Polymalic Acid Tritryptophan Copolymer Interacts with Lipid Membrane Resulting in Membrane Solubilization. (21st May 2017)

• Record Type: Journal Article
• Authors: Ding, Hui; Fox, Irving; Patil, Rameshwar; Galstyan, Anna; Black, Keith L.; Ljubimova, Julia Y.; Holler, Eggehard
• Other Names: Omri Abdelwahab Academic Editor.
• Is Part Of: Journal of nanomaterials. Volume 2017(2017)
• Publication Date: 2017-05-21
• Subjects: Nanostructured materials -- Periodicals; Nanotechnology -- Periodicals; Nanomatériaux; Nanostructured materials; Nanotechnology; Nanostructures; Nanotechnology; Periodicals; Fulltext; Internet Resources; Periodicals; 620.115
• DOI: 10.1155/2017/4238697
• Languages: English
• ISSNs: 1687-4110

Abstract

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.