Polyunsaturated chains in asymmetric lipids disorder raft mixtures and preferentially associate with α-Synuclein

Benjamin E. Brummel, Anthony R. Braun, Jonathan N. Sachs

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Using molecular dynamics simulations, we have explored the effect of asymmetric lipids—specifically those that contain one polyunsaturated (PUFA) and one saturated fatty acid chain—on phase separation in heterogeneous membranes. These lipids are prevalent in neuronal membranes, particularly in synaptic membranes, where the Parkinson's Disease protein α-Synuclein (αS) is found. We have therefore explored the relationship between asymmetric, PUFA-containing lipids, and αS. The simulations show that asymmetric lipids partition to the liquid disordered (Ld) phase of canonical raft mixtures because of the highly disordered PUFA chain. In the case of a membrane built to mimic the lipid composition of a synaptic vesicle, the PUFA-containing asymmetric lipids completely disrupt phase separation. Because αS is positively charged, we show that it partitions with negatively charged lipids, regardless of the saturation state of the chains. Additionally, αS preferentially associates with the polyunsaturated fatty acid tails of both charged and neutral lipids. This is a consequence of those chains’ ability to accommodate the void beneath the amphipathic helix. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number4
StatePublished - Apr 1 2017

Bibliographical note

Funding Information:
This study was funded by the National Institutes of Health R01 NS084998-01 to J.N.S.

Publisher Copyright:
© 2016


  • Amphipathic helices
  • Lipid rafts
  • Molecular dynamics simulations
  • Phase separation
  • Polyunsaturated fatty acids
  • α-Synuclein


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