Intrinsic Determinants of Aβ pH-Dependent Self-Assembly Revealed by Combined Computational and Experimental Studies
2011

How pH Affects Amyloid Beta Peptide Self-Assembly

publication 10 minutes Evidence: moderate

Author Information

Author(s): Xu Weixin, Zhang Ce, Derreumaux Philippe, Gräslund Astrid, Morozova-Roche Ludmilla, Mu Yuguang

Primary Institution: State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China

Hypothesis

The study investigates how pH influences the self-assembly of amyloid beta peptides into fibrils.

Conclusion

The research shows that pH 5.0 is the most favorable condition for amyloid formation, while pH 8.4 significantly inhibits it.

Supporting Evidence

  • At pH 5.0, the amyloid self-assembly proceeded rapidly, leading to a dense network of fibrils.
  • At pH 2.9, amyloid fibrils were shorter and less abundant than at pH 5.0.
  • At pH 8.4, amyloid formation was significantly depressed, with low fluorescence and unstructured aggregates observed.

Takeaway

This study found that changing the acidity of the environment can change how proteins stick together, which is important for understanding diseases like Alzheimer's.

Methodology

The study used molecular dynamics simulations and experimental techniques like ThT binding assays and atomic force microscopy to analyze the self-assembly of amyloid beta peptides at different pH levels.

Limitations

The study's findings may not fully represent the complex biological environment of the human brain.

Digital Object Identifier (DOI)

10.1371/journal.pone.0024329

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