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Fast Probing Amyloid Polymorphism via Nanopore Translocation.

Lijian Zhan1,2, Tonghui Jin3, Jiangtao Zhou3

  • 1Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland.

Nano Letters
|October 19, 2023
PubMed
Summary
This summary is machine-generated.

This study presents a new nanopore method for detecting amyloid fibril structures in neurodegenerative diseases. The technique rapidly screens fibril polymorphism, aiding in early diagnosis and differentiation of amyloid aggregates.

Keywords:
amyloidlysozymenanoporepolymorphismβ-lactoglobulin

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Area of Science:

  • Biophysics
  • Nanotechnology
  • Neuroscience

Background:

  • Neurodegenerative diseases feature cross-β-sheet amyloid fibrils with complex polymorphism.
  • Noninvasive detection of these fibrils with high fidelity is crucial for diagnosis.
  • Current detection methods can have artifacts and limitations in characterizing fibril polymorphism.

Purpose of the Study:

  • To introduce a sensitive synthetic nanopore methodology for probing amyloid fibril polymorphism.
  • To develop an automated and fast screening protocol for analyzing amyloid structures.
  • To enable physical discrimination and separation of amyloid fibrils for diagnostic purposes.

Main Methods:

  • Utilizing a sensitive synthetic nanopore to analyze translocation events of amyloid fibrils.
  • Statistically analyzing current block amplitude and dwell time during fibril translocation.
  • Correlating nanopore data with atomic force microscopy observations of amyloid polymorphs.

Main Results:

  • The nanopore method successfully extracted the cross-sectional configuration of hydrated amyloid fibrils.
  • Dwell time analysis correlated with fibril length, providing structural insights.
  • Single translocation events revealed abnormal amyloid conformations, overcoming microscopy artifacts.

Conclusions:

  • The synthetic nanopore approach offers an effective method for discriminating and separating amyloid fibrils.
  • This technique holds potential for the rapid diagnosis of early aggregating pathological amyloidosis.
  • The study advances noninvasive detection of amyloid fibril polymorphism in neurodegenerative diseases.