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Biomacromolecules. 2018 Mar 12;19(3):761-772. doi: 10.1021/acs.biomac.7b01539. Epub 2018 Jan 16.

Influence of Poly(styrene- co-maleic acid) Copolymer Structure on the Properties and Self-Assembly of SMALP Nanodiscs.

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School of Biosciences , University of Birmingham , Edgbaston, Birmingham B15 2TT , United Kingdom.
Diamond Light Source , Harwell Science and Innovation Campus , Didcot OX11 ODE , United Kingdom.
Department of Chemistry , University of Bath , Claverton Down , Bath BA2 7AY , United Kingdom.
ISIS Neutron and Muon Source, Science and Technology Facilities Council Rutherford Appleton Laboratory , Harwell, Didcot OX11 0QX , United Kingdom.
Department of Chemistry and Polymer Science, Division of Polymer Science , Stellenbosch University , De Beers Street , Stellenbosch 7600 , South Africa.


Polymer stabilized nanodiscs are self-assembled structures composed of a polymer belt that wraps around a segment of lipid bilayer, and as such are capable of encapsulating membrane proteins directly from the cell membrane. To date, most studies on these nanodiscs have used poly(styrene- co-maleic acid) (SMA) with the term SMA-lipid particles (SMALPs) coined to describe them. In this study, we have determined the physical and thermodynamic properties of such nanodiscs made with two different SMA copolymers. These include a widely used and commercially available statistical poly(styrene- co-maleic acid) copolymer (coSMA) and a reversible addition-fragmentation chain transfer synthesized copolymer with narrow molecular weight distribution and alternating styrene and maleic acid groups with a polystyrene tail, (altSMA). We define phase diagrams for each polymer, and show that, regardless of polymer topological structure, self-assembly is driven by the free energy change associated with the polymers. We also show that nanodisc size is polymer dependent, but can be modified by varying polymer concentration. The thermal stability of each nanodisc type is similar, and both can effectively solubilize proteins from the E. coli membrane. These data show the potential for the development of different SMA polymers with controllable properties to produce nanodiscs that can be optimized for specific applications and will enable more optimized and widespread use of the SMA-based nanodiscs in membrane protein research.

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