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Fluorinated surfactants comprise a polar head group and a fluorinated hydrophobic tail. These surfactants are unique in that they are not miscible with lipids, meaning unlike their hydrogenated counterparts, fluorinated surfactants are unable to directly solubilize a membrane protein from the native lipid bilayer. Fluorinated surfactants have a number of useful applications for protein biochemistry, ranging from improving membrane protein stability, aiding the vitrification process in single-particle electron cryo-microscopy (Cryo-EM), and as an additive in protein crystallization.
 
Membrane Protein Stability:
 
Often, the first step in working with membrane proteins involves the solubilization of the protein from the native lipid bilayer using detergents, such as DDM, DM, OG, and LDAO, among many others(1). One disadvantage of working with detergents is that they tend to strip native lipids away from the protein, as well as possibly interfering with helix-helix interactions in the transmembrane domain, both of which could destabilize / inactivate the protein(2). There has been much research into the design of surfactants that a membrane protein can be exchanged into after solubilization that will keep it soluble and functional(3). Some of these molecules include Amphipols, Tripod Amphipiles, and Fluorinated Surfactants.  The current hypotheses of why fluorinated surfactants are less likely to destabilize membrane proteins are: 1) that micelles of fluorinated surfactants do not behave like a “hydrophobic sink” and will not attract natively bound lipids and cofactors and 2) fluorinated tails have reduced affinity for transmembrane helices and will not disrupt the helix-helix interactions(4)
 
Cryo-EM Sample Preparation:
 
We are currently witnessing the emergence of single-particle electron cryo-microscopy(5) as a powerful technique for determining atomic resolution structures of proteins. Over half of the total number of Cryo-EM structures have been deposited in the past three years alone. The main sample preparation step in a Cryo-EM experiment is dispensing a protein solution onto a carbon grid followed by plunge freezing, creating a thin layer of vitreous ice. To our knowledge, four Cryo-EM structures of membrane proteins have utilized fluorinated surfactants in the sample buffer to improve the vitrification process: the ryanodine receptor RyR1 (0.2% Fluorinated OM)(6), the Tc toxin TcdA1 (0.01% Fluorinated OM)(7), the multidrug resistance protein, MRP1 (3 mM Fluorinated FC-8)(8), and the Cystic Fibrosis Transmembrane Conductance Regulator (3 mM Fluorinated FC-8)(9). According to the authors of these studies, these fluorinated surfactants improved the distribution of protein molecules in the vitreous ice and/or improve the ice thickness distribution of the grids.
 
Crystallization Additive:
 
As an additive for protein crystallization, detergents can reduce the amount of non-specific aggregation of a protein sample, which can prevent sample crystallization(10). For this application, detergents are usually added to reservoir solution at concentrations at or below their critical micelle concentration. The fluorinated surfactants Fos-Choline 8 and Octyl Maltoside are typically included in commercially available detergent screening kits. These fluorinated surfactants have been used successfully in the crystallization of a number of proteins. Some examples include the Complex of Cytochrome c and Cytochrome c Oxidase (0.7% Fluorinated OM)
(11), Respiratory Complex 1 (2.04 mM Fluorinated OM)(12), Thrioredoxin-fold protein (2.2 mM Fluorinated FC-8)(13), and the Aminotransferase Ald1 (2.2 mM Fluorinated FC-8)(14).

References:

1. Wiener, M. C. (2004) Methods 34(3), 364-372.
2. Breyton, C., et. al (2004) FEBS Lett. 564(3), 312-318.
3. Frotscher, E., et. al (2015) Angew Chem Int Ed Engl. 54(17), 5069-5073.
4. Popot, J. L. (2010) Annu Rev Biochem. 79, 737-775.
5. Milne, J. L., et. al (2013) FEBS J. 280(1), 28-45.
6. Efremov, R. G., et. al (2015) Nature 517(7532), 39-43.
7. Gatsogiannis, C., et. al (2016) Nat Struct Mol Biol. 23(10), 884-890.
8. Johnson, Z. L. and Chen, J (2017) Cell 168(6), 1075-1085.
9. Zhang, Z. and Chen, J. (2016) Cell 167(6), 1586-1597.
10. McPherson, A. and Cudney B. Acta Crystallogr F Struct Biol Commun. 70(Pt 11), 1445-1467.
11. Shimada, S., et. al (2017) EMBO J. 36(3), 291-300.
12. Efremov, R. G., et. al (2010) Nature 465(7297), 441-445.
13. Yoon, J. Y., et. al (2013) Acta Crystallogr D Biol Crystallogr. 69(Pt 5), 735 – 746.
14. Sobolev, V., et. al (2013) Acta Crystallogr Sect F Struct Biol Cryst Commun. 69(Pt 2), 84-89.