Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution

J Phys Chem B. 2019 May 30;123(21):4562-4570. doi: 10.1021/acs.jpcb.9b03681. Epub 2019 May 16.

Abstract

The absence of detergent and curvature makes nanodiscs excellent membrane mimetics. The lack of structural and mechanistic model of polymer-encapsulated lipid nanodiscs limits their use in the study of the structure, dynamics, and functions of membrane proteins. In this study, we parameterized and optimized the coarse-graining (CG) bead mapping for two differently charged and functionalized copolymers, containing styrene-maleic acid (SMAEA) and polymethacrylate (PMAQA), for the Martini force-field framework and showed nanodisc formation (<8 nm diameter) on a time scale of tens of microseconds using molecular dynamics (MD) simulations. Structural models of ∼2.0 or 4.8 kDa PMAQA and ∼2.2 kDa SMAEA polymer-based lipid nanodiscs highlight the importance of the polymer chemical structure, size, and polymer-lipid ratio in the optimization of the nanodisc structure. The ideal spatial arrangement of polymers in nanodiscs, nanodisc size, and thermal stability obtained from our MD simulation correlates well with the experimental observations. The polymer-nanodiscs were tested for the reconstitution of single-pass or multipass transmembrane proteins. We expect this study to be useful in the development of novel polymer-based lipid nanodiscs and for the structural studies of membrane proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / chemistry*
  • Dimyristoylphosphatidylcholine / chemistry
  • Humans
  • Integrin beta3 / chemistry*
  • Lipid Bilayers / chemistry
  • Maleates / chemistry*
  • Molecular Dynamics Simulation
  • Nanoparticles / chemistry*
  • Nostoc / chemistry
  • Phosphatidylcholines / chemistry
  • Polymethacrylic Acids / chemistry*
  • Polystyrenes / chemistry*
  • Rhodopsins, Microbial / chemistry*

Substances

  • Amyloid beta-Protein Precursor
  • Integrin beta3
  • Lipid Bilayers
  • Maleates
  • Phosphatidylcholines
  • Polymethacrylic Acids
  • Polystyrenes
  • Rhodopsins, Microbial
  • 1,2-dilauroylphosphatidylcholine
  • styrene-maleic acid polymer
  • Dimyristoylphosphatidylcholine