Recent Advances on Polymer Lipid Particles (PoLP) in Membrane Protein Research


Membrane proteins (MPs) structure elucidation is of crucial importance as they represent a major target for drug design. However, owing to their high hydrophobicity, MPs are challenging proteins to study. The use of polymer lipid nanoparticles (PoLP) has recently allowed a leap forward in the field of MP research. A wide range of polymers have been successfully used for elucidating the structure of MPs. One polymer in particular, styrene maleic acid (SMA) copolymer, is recently catching a large interest owing to its easy use in detergentā€free membrane solubilisation and the recent successes in purification and stabilising MPs for further biophysical studies.

Key Concepts

  • SMA copolymers are new tools to purify membrane proteins.
  • SMA copolymers can solubilise membrane proteins directly without the need of detergents.
  • Membrane proteins purified in SMALP are stable over time and remain active owing to the retention of native lipids around the proteins.
  • SMA use limitations include acid pH sensitivity, divalent cations sensitivity and UV absorption.
  • New polymers (SMA and others) are being engineered to overcome these limitations.

Keywords: membrane protein; polymer; styrene; maleic acid; SMA; nanoparticles; PoLP

Figure 1. Schematic of the polymerisation and alkaline hydrolysis events leading to the formation of the styrene maleimide copolymer 2:1.
Figure 2. Solubilisation stages and nanoparticle generation. (a) Representation of a membrane protein in a SMA nanoparticle. (b) Schematic of the putative steps involved in the solubilisation of membranes by SMA copolymer to form nanoparticles.
Figure 3. Purification of membrane protein with SMA copolymer solubilisation. Schematic explaining the various steps of SMA solubilisation of membranes, nanoparticle generation, purifcation via a His‐tag (red star) on the protein of interest and further particle analysis.


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Further Reading

Esmaili M and Overduin M (2018) Membrane biology visualized in nanometer‐sized discs formed by styrene maleic acid polymers. Biochimica et Biophysica Acta 1860 (2): 257–263.

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de Marcos Lousa, Carine, and Postis, Vincent(Jul 2018) Recent Advances on Polymer Lipid Particles (PoLP) in Membrane Protein Research. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0027944]