Effect of Polymer Composition and pH on Membrane Solubilization by Styrene-Maleic Acid Copolymers.
The styrene-maleic acid (SMA) copolymer is rapidly gaining attention as a tool in membrane research, due to its ability to directly solubilize lipid membranes into nanodisk particles without the requirement of conventional detergents. Although many variants of SMA are commercially available, so far only SMA variants with a 2:1 and 3:1 styrene-to-maleic acid ratio have been used in lipid membrane studies. It is not known how SMA composition affects the solubilization behavior of SMA. Here, we systematically investigated the effect of varying the styrene/maleic acid on the properties of SMA in solution and on its interaction with membranes. Also the effect of pH was studied, because the proton concentration in the solution will affect the charge density and thereby may modulate the properties of the polymers. Using model membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine lipids at pH > pHagg, we found that membrane solubilization is promoted by a low charge density and by a relatively high fraction of maleic acid units in the polymer. Furthermore, it was found that a collapsed conformation of the polymer is required to ensure efficient insertion into the lipid membrane and that efficient solubilization may be improved by a more homogenous distribution of the maleic acid monomer units along the polymer chain. Altogether, the results show large differences in behavior between the SMA variants tested in the various steps of solubilization. The main conclusion is that the variant with a 2:1 styrene-to-maleic acid ratio is the most efficient membrane solubilizer in a wide pH range.
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: s.scheidelaar@uu.nl.
Stefan
S
Scheidelaar
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Martijn C
MC
Koorengevel
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Cornelius A
CA
van Walree
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Juan J
JJ
Dominguez
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Jonas M
JM
Dörr
Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: j.a.killian@uu.nl.
J Antoinette
JA
Killian
D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008298:Maleates / Q000737:chemistry*; D008823:Micelles; D011137:Polystyrenes / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility
D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C024075:styrofoam; C030272:maleic acid; D004134:Dimyristoylphosphatidylcholine