Non-ionic detergents contain uncharged hydrophilic glucose-derived or polyoxyethylene head groups. This type of detergent is considered to be mild as the destabilization they cause is almost completely reversible. This capacity is explained by the fact that non-ionic detergents typically disrupt protein-lipid (and lipid-lipid) but not protein-protein interactions, thus maintaining (or better to phrase—not interfering with) the native state of a protein. Based on this, the primary application of non-ionic detergents is in the study of various biologically active forms of membrane proteins. However, the degree of destabilization correlates well with the length of the acyl chain of the detergent. In this regard, short (C7–C10) hydrocarbon chains (e.g., octylglucoside and nonylmaltoside) can often lead to deactivation of the protein, in contrast to their corresponding intermediate (C12–C14) chain-length derivatives (e.g., dodecylmaltoside) [1].
Fig. 1. The non-ionic detergents micelle.
Non-ionic detergents can be further classified into two types: polyoxyethylene (and related detergents), and glycosidic detergents.
Fig. 2. Structure of Triton X-100.
Fig. 3. Structure of n-dodecyl-β-D-maltoside.
Due to the mild and nondenaturing characteristics of non-ionic detergents, they are frequently used in studies of membrane proteins when compared to other applications. It is reported that a majority of the detergents used in the purification and structural determination of membrane proteins are non-ionic detergents. According to the report from Stetsenko et al., the non-ionic detergents account for a large part of the top 10 detergents used for the structural analysis of membrane proteins [2]. They are n-dodecyl-β-D-maltopyranoside (DDM), n-decyl-β-D-maltopyranoside (DM), n-octyl-β-D-glucopyranoside (OG), n-nonyl β-D-glucopyranoside (NG), polyoxyethylene 8 dodecyl ether (C12E8), n-undecyl-β-D-maltopyranoside (UM or UDM), lauryl maltose neopentyl glycol (LMNG or MNG-3), Triton X-100 and digitonin, respectively. And DDM, DM, and OG dominate, both for purification and crystallization. Looking at the results, one can confidently say that the non-ionic detergents rule the field of structural studies on membrane proteins. In addition, according to the result of statistics analysis, DDM and DM are reported as the detergents of choice for more than a half of structural studies on membrane proteins. With an addition of UDM, Cymal-5, Cymal-6, OG and NG, the total fraction of sugar-based detergents is around 75% of structural studies on membrane proteins.
Fig. 4. The bar representation (in %) of different detergents used for (A) membrane proteins purification and (B) crystallization (up to 31 December 2016).
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