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Updated: Feb 20, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

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Membrane Binding and Pore Formation by a Cytotoxic Fragment of Amyloid β Peptide

Nabin Kandel, Tianyu Zheng, Qun Huo

  • 1Department of Physics, University of Central Florida , Physical Sciences Bldg., Room 456, 4111 Libra Drive, Orlando, Florida 32816, United States.

The Journal of Physical Chemistry. B
|October 18, 2017
PubMed

Insights

Amyloid beta (Aβ) peptide fragment Aβ25-35 forms pores in cell membranes, contributing to Alzheimer's disease neurotoxicity. Biophysical studies reveal electrostatic interactions and beta-sheet structure are crucial for this pore formation mechanism.

Area of Science:

  • Neuroscience
  • Biophysics
  • Biochemistry

Background:

  • Alzheimer's disease pathogenesis involves Amyloid beta (Aβ) peptides.
  • The Aβ25-35 fragment is a neurotoxic Aβ form implicated in Alzheimer's disease.
  • Aβ25-35-induced neurotoxicity may involve mitochondrial dysfunction and calcium (Ca2+) permeable pore formation.

Purpose of the Study:

  • To biophysically characterize the membrane binding and pore formation activity of the Aβ25-35 peptide.
  • To elucidate the mechanism underlying Aβ25-35-induced membrane pore formation and Ca2+ influx.

Main Methods:

  • Microelectrophoresis was used to analyze Aβ25-35 interaction with anionic and zwitterionic membranes.
  • Quin-2 loaded vesicles were used to monitor Ca2+ influx, indicating pore formation.
  • Circular dichroism spectroscopy assessed the secondary structure of Aβ25-35 during pore formation.

Main Results:

  • Aβ25-35 binding and pore formation were suppressed by decreased membrane anionic charge and high ionic strength, highlighting the role of electrostatic interactions.
  • Circular dichroism revealed that Aβ25-35 adopts a β-sheet conformation when forming the most efficient pores.
  • The data support an oligo-oligomeric pore model comprising up to eight peptide units, each with 6-8 monomers.

Conclusions:

  • Aβ25-35 peptide forms Ca2+-permeable pores in cell membranes, a key mechanism in its neurotoxicity.
  • Electrostatic interactions and the β-sheet conformation of Aβ25-35 are critical for membrane binding and pore formation.
  • The findings provide insights into the structural basis of Aβ-mediated membrane disruption in Alzheimer's disease.

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