Assembly of α-synuclein aggregates on phospholipid bilayers

Zhengjian Lv, Mohtadin Hashemi, Siddhartha Banerjee, Karen Zagorski, Jean Christophe Rochet, Yuri L. Lyubchenko

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The spontaneous self-assembly of α-synuclein (α-syn) into aggregates of different morphologies is associated with the development of Parkinson's disease. However, the mechanism behind the spontaneous assembly remains elusive. The current study shows a novel effect of phospholipid bilayers on the assembly of the α-syn aggregates. Using time-lapse atomic force microscopy, it was discovered that α-syn assembles into aggregates on bilayer surfaces, even at the nanomolar concentration range. The efficiency of the aggregation process depends on the membrane composition, with the greatest efficiency observed for of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS). Importantly, assembled aggregates can dissociate from the surface, suggesting that on-surface aggregation is a mechanism by which pathological aggregates may be produced. Computational modeling revealed that dimers of α-syn assembled rapidly, through the membrane-bound monomer on POPS bilayer, due to an aggregation-prone orientation of α-syn. Interaction of α-syn with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) leads to a binding mode that does not induce a fast assembly of the dimer. Based on these findings, we propose a model in which the interaction of α-syn with membranes plays a critical role initiating the formation of α-syn aggregates and the overall aggregation process.

Original languageEnglish (US)
Pages (from-to)802-812
Number of pages11
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number9
StatePublished - Sep 2019


  • Amyloid aggregation
  • Computer modeling
  • Lipid bilayer
  • Parkinson's disease
  • Time-lapse AFM
  • α-synuclein

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology


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