Atomic Insights into Amyloid-Induced Membrane Damage

Yanxing Yang, Hannah Distaffen, Sharareh Jalali, Andrew J. Nieuwkoop, Bradley L. Nilsson, Cristiano L. Dias

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Amphipathic peptides can cause biological membranes to leak either by dissolving their lipid content via a detergent-like mechanism or by forming pores on the membrane surface. These modes of membrane damage have been related to the toxicity of amyloid peptides and to the activity of antimicrobial peptides. Here, we perform the first all-atom simulations in which membrane-bound amphipathic peptides self-assemble into β-sheets that subsequently either form stable pores inside the bilayer or drag lipids out of the membrane surface. An analysis of these simulations shows that the acyl tail of lipids interact strongly with non-polar side chains of peptides deposited on the membrane. These strong interactions enable lipids to be dragged out of the bilayer by oligomeric structures accounting for detergent-like damage. They also disturb the orientation of lipid tails in the vicinity of peptides. These distortions are minimized around pore structures. We also show that membrane-bound β-sheets become twisted with one of their extremities partially penetrating the lipid bilayer. This allows peptides on opposite leaflets to interact and form a long transmembrane β-sheet, which initiates poration. In simulations, where peptides are deposited on a single leaflet, the twist in β-sheets allows them to penetrate the membrane and form pores. In addition, our simulations show that fibril-like structures produce little damage to lipid membranes, as non-polar side chains in these structures are unavailable to interact with the acyl tail of lipids.

Original languageEnglish (US)
Pages (from-to)2766-2777
Number of pages12
JournalACS Chemical Neuroscience
Volume13
Issue number18
DOIs
StatePublished - Sep 21 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Keywords

  • amyloid
  • detergent-like effect
  • lipid membrane
  • membrane damage
  • poration

Fingerprint

Dive into the research topics of 'Atomic Insights into Amyloid-Induced Membrane Damage'. Together they form a unique fingerprint.

Cite this