Pro-inflammatory protein S100A9 alters membrane organization by dispersing ordered domains

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1865; no. 3; p. 184113
• Main Authors: Tamulytė, Rimgailė, Jankaitytė, Evelina, Toleikis, Zigmantas, Smirnovas, Vytautas, Jankunec, Marija
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023
• Subjects: Aggregation; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Atomic force microscopy; Brain - metabolism; Humans; Lipid Bilayers - chemistry; Lipid membrane remodeling; Nuclear Proteins - metabolism; Phase separation; S100A9; Tethered lipid bilayers; Aggregation; Atomic force microscopy; Lipid membrane remodeling; Tethered lipid bilayers; S100A9; Phase separation
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2022.184113

Pro-inflammatory, calcium-binding protein S100A9 is localized in the cytoplasm of many cells and regulates several intracellular and extracellular processes. S100A9 is involved in neuroinflammation associated with the pathogenesis of Alzheimer's disease (AD). The number of studies on the impact of S100A9 in co-aggregation processes with amyloid-like proteins is increasing. However, there is still a lack of data on how this protein interacts with lipid membranes. We employed atomic force microscopy (AFM), dynamic light scattering (DLS), and fluorescence measurements (Laurdan and Thioflavin-T) to study the interaction between protein and the membrane surface. We used lipid vesicles in bulk and planar tethered lipid bilayers as biomimetic membrane models. We demonstrated that the protein accumulates on negatively charged lipid bilayers but with no further loss of the bilayer's integrity. The most important result is that the initial adsorption and accumulation of apo-form of S100A9 on the lipid membrane surface is lipid phase-sensitive. The breaking down of raft-like and disappearance of gel-like domains indicate that protein incorporates into the hydrophobic part of the lipid bilayer. We observed the most noticeable loss of integrity in lipid bilayers constructed from a lipid mixture (brain total lipid extract). Understanding the function and interactions of these proteins in cellular environments might expand the development of new diagnostic and therapeutic approaches for AD or other related diseases. [Display omitted] •In a calcium-free environment, the lipid bilayer affects a pro-inflammatory S100A9 protein's accumulation and aggregation.•S100A9 in apo-form can interact with cell membranes to induce membrane remodeling via different mechanisms.•Brain total lipid extract lipid bilayers lose their integrity spontaneously after adding S100A9.