| Abstract [eng] |
Neuronal cell death induced by cell membrane damage is one of the major hallmarks of neurodegenerative diseases. Neuroinflammation precedes the loss of neurons; however, whether and how inflammation-related proteins contribute to the loss of membrane integrity remains poorly understood. This study aimed to investigate the interactions of the proinflammatory proteins S100A8, S100A9, and the S100A8/A9 complex with an artificial lipid bilayer mimicking the neuronal plasma membrane. For the first time, it was demonstrated that direct interactions of S100A8, S100A9, and the S100A8/A9 complex with an anionic membrane compromise lipid bilayer integrity. High-speed atomic force microscopy enabled real-time observation of morphological changes induced by S100A8 and S100A8/A9, indicating that membrane disruption proceeds via a detergent-like mechanism. In contrast, conventional atomic force microscopy demonstrated that insertion of S100A9 into the membrane induces lateral expansion of lipid molecules and reduces membrane mechanical stiffness. Furthermore, it was found that changes in membrane composition significantly influence S100 protein aggregation and the potential formation of neurotoxic assemblies. These findings not only enhance our understanding of the links between inflammation and neurodegeneration but also may facilitate the development of novel diagnostic and therapeutic strategies. |
