Exogenous polyserine fibrils change membrane properties of phosphatidylcholine-liposome and red blood cells

• Published in: Biochimica et biophysica acta. Biomembranes 2024-06, Vol.1866 (5), p.184331, Article 184331
• Main Authors: Iizuka, Yutaro, Katano-Toki, Akiko, Hayashi, Fumio, Fujioka, Jun, Takahashi, Hiroshi, Nakamura, Kazuhiro
• Format: Article
• Language: English
• Subjects: Aggregation; Cell Membrane - chemistry; Cell Membrane - drug effects; Cell Membrane - metabolism; Differential scanning calorimetry; Erythrocytes - drug effects; Erythrocytes - metabolism; Humans; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Liposome; Liposomes - chemistry; Peptides - chemistry; Peptides - pharmacology; Phase Transition; Phosphatidylcholines - chemistry; Polyglutamine; Red blood cell; Repeat-associated non-AUG translation
• ISSN: 0005-2736; 1879-2642; 1879-2642
• DOI: 10.1016/j.bbamem.2024.184331

The causative genes for neurodegenerative polyglutamine (polyQ) diseases produce homopolymeric polyglutamine (polyQ), polyserine (polyS), polyalanine (polyA), polycysteine (polyC), and polyleucine (polyL) sequences by repeat-associated non-AUG (RAN) translation. The cytotoxicity of the intracellular polyQ and RAN products has been extensively investigated. However, little is known about the toxicity of the extracellular polyQ and RAN products on the membranes of viable cells. Because polyQ aggregates induce a deflated morphology of a model membrane, we hypothesized that extracellular polyQ and RAN products might affect the membrane properties of viable cells. In this study, we demonstrated that exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the thermal phase transition behavior of a model membrane composed of a phosphatidylcholine bilayer using differential scanning calorimetry. PolyS fibrils induced morphological changes in viable red blood cells (RBCs). However, both polyS and polyQ non-fibril aggregates had no effects on RBCs. These results highlight the possibility that extracellular fibrils generated from RAN products may alter the properties of neuronal cell membranes, which may contribute to changes in the brain pathology. [Display omitted] •Exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the main transition temperature.•PolyS fibrils have no effect on the transition width or transition enthalpy.•PolyS fibrils specifically induced morphological changes in viable red blood cells.