Detergents as Tools in Membrane Biochemistry

Detergents are invaluable tools for studying membrane proteins. However, these deceptively simple, amphipathic molecules exhibit complex behavior when they self-associate and interact with other molecules. The phase behavior and assembled structures of detergents are markedly influenced not only by their unique chemical and physical properties but also by concentration, ionic conditions, and the presence of other lipids and proteins. In this minireview, we discuss the various aggregate forms detergents assume and some misconceptions about their structure. The distinction between detergents and the membrane lipids that they may (or may not) replace is emphasized in the most recent high resolution structures of membrane proteins. Detergents are clearly friends and foes, but with the knowledge of how they work, we can use the increasing variety of detergents to our advantage. Detergents are invaluable tools for studying membrane proteins. However, these deceptively simple, amphipathic molecules exhibit complex behavior when they self-associate and interact with other molecules. The phase behavior and assembled structures of detergents are markedly influenced not only by their unique chemical and physical properties but also by concentration, ionic conditions, and the presence of other lipids and proteins. In this minireview, we discuss the various aggregate forms detergents assume and some misconceptions about their structure. The distinction between detergents and the membrane lipids that they may (or may not) replace is emphasized in the most recent high resolution structures of membrane proteins. Detergents are clearly friends and foes, but with the knowledge of how they work, we can use the increasing variety of detergents to our advantage. critical micelle concentration protein-detergent complex lower consolute β-d-octyl glucoside upper consolute Over the past decade, our understanding of the structure and function of membrane proteins has advanced significantly as well as how their detailed characterization can be approached experimentally. Detergents have played significant roles in this effort. They serve as tools to isolate, solubilize, and manipulate membrane proteins for subsequent biochemical and physical characterization. Many of the successful methods for reconstituting (1Rigaud J.L. Pitard B. Levy D. Biochim. Biophys. Acta. 1995; 1231: 223-246Crossref PubMed Scopus (409) Google Scholar) and crystallizing (2Garavito R.M. Markovic-Housley Z. Jenkins J.A. J. Crystal Growth. 1986; 76: 701-709Crossref Scopus (70) Google Scholar, 3Garavito R.M. Picot D. Loll P.J. J. Bioenerg. Biomembr. 1995; 28: 13-27Crossref Scopus (108) Google Scholar, 4Kühlbrandt W. Q. Rev. Biophys. 1988; 21: 429-477Crossref PubMed Scopus (139) Google Scholar) membrane proteins rely on the unique behavior of detergents. Although many new detergents are now available for use with membrane proteins, their behavior in solution and in the presence of protein may limit their use with specific experimental techniques. Hence, the choice of detergent and experimental conditions will have an enormous impact on whether a technique can be successfully applied to a specific membrane protein. A clear understanding of basic detergent behavior and of the structure of micelles and protein-detergent complexes is thus crucial for membrane biochemists. In this minireview, we will briefly discuss the basic aspects of detergent physical chemistry that affect membrane proteins and their manipulation in the context of the new information about membrane protein structure and function. The reader is directed to comprehensive reviews by Helenius and Simons (5Helenius A. Simons K. Biochim. Biophys. Acta. 1975; 415: 69-79Crossref Scopus (2440) Google Scholar), Tanford and Reynolds (6Tanford C. Reynolds J.A. Biochim. Biophys. Acta. 1976; 457: 133-170Crossref PubMed Scopus (679) Google Scholar), Helenius et al. (7Helenius A. McCaslin D.R. Fries E. Tanford C. Methods Enzymol. 1979; 56: 734-749Crossref PubMed Scopus (609) Google Scholar), Kühlbrandt (4Kühlbrandt W. Q. Rev. Biophys. 1988; 21: 429-477Crossref PubMed Scopus (139) Google Scholar), and Zulauf (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar), which cover the action and behavior of detergents from a biochemical viewpoint. Excellent monographs by Tanford (9Tanford C. The Hydrophobic Effect. John Wiley & Sons, Inc., New York1980Google Scholar) and Rosen (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar), as well as a review by Wennerström and Lindman (11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar), describe the physical chemistry of detergents and surfactants in detail. Detergents are surface-active molecules that self-associate and bind to hydrophobic surfaces in a concentration-dependent manner (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar). The amphipathic character of detergents is evident in their structures (Fig. 1a), which consist of a polar (or charged) head group and a hydrophobic tail. Most detergents fall into one of three categories depending on the type of head group: ionic (cationic or anionic), nonionic, and zwitterionic. The behavior of a specific detergent is dependent on the character and stereochemistry of the head group and tail. In the broader sense, detergents and lipids are both surfactants. What distinguishes one from the other are the concentration regimes for self-association and the kinds of multimolecular structures each can make. The problem of isolating native membrane proteins from lipid bilayers and then subsequently manipulating them is, in essence, a problem of dealing with mixed surfactant systems. The most common question about detergent use is whether a “magic bullet” detergent exists. The simple answer is no, but successful strategies for detergent use do exist. The key to a successful experiment is to understand how detergents and lipids impact the physical nature of a protein-detergent-lipid complex and its behavior. Detergent monomers in aqueous solutions are involved in two kinds of basic phase transitions. First, monomers can crystallize in aqueous solution (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar), although the majority of detergents used in membrane biochemistry do not (4Kühlbrandt W. Q. Rev. Biophys. 1988; 21: 429-477Crossref PubMed Scopus (139) Google Scholar, 5Helenius A. Simons K. Biochim. Biophys. Acta. 1975; 415: 69-79Crossref Scopus (2440) Google Scholar, 6Tanford C. Reynolds J.A. Biochim. Biophys. Acta. 1976; 457: 133-170Crossref PubMed Scopus (679) Google Scholar, 7Helenius A. McCaslin D.R. Fries E. Tanford C. Methods Enzymol. 1979; 56: 734-749Crossref PubMed Scopus (609) Google Scholar). Second, detergent monomers self-associate to form structures called micelles (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar). At a broad threshold of monomer concentration called the critical micelle concentration (CMC)1 (Fig.1 b), self-association occurs and micelles form. Ideally, the concentration of detergent monomers stays constant above the CMC as more detergent is added to the solution; only the concentration of micelles increases (12Gunnarsson G. Jönsson B. Wennerström H. J. Phys. Chem. 1980; 84: 3114-3121Crossref Scopus (368) Google Scholar). When the concentration exceeds the CMC, a detergent becomes capable of solubilizing hydrophobic and amphipathic molecules, such as lipids, into mixed micelles or micellar aggregates (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar). Moreover, the complete and stable solubilization of many integral membrane proteins generally occurs above the CMC, as the detergent associates with the hydrophobic surfaces of membrane proteins to create water-soluble protein-detergent complexes (PDCs) (13Haneskog L. Andersson L. Brekkan E. Englund A.K. Kameyama K. Liljas L. Greijer E. Fischbarg J. Lundahl P. Biochim. Biophys. Acta. 1996; 1282: 39-47Crossref PubMed Scopus (20) Google Scholar, 14le Maire M. Kwee S. Andersen J. Møller J. Eur. J. Biochem. 1983; 129: 525-532Crossref PubMed Scopus (67) Google Scholar, 15Marone P.A. Thiyagarajan P. Wagner A.M. Tiede D.M. J. Crystal Growth. 1999; 207: 214-225Crossref Scopus (23) Google Scholar). Micellarization is a common phenomenon with many surfactants. The average size and shape of micelles depend on the type, size, and stereochemistry of the surfactant monomer (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar) as well as the solvent environment. The size of a micelle can be described by its average molecular weight, hydrodynamic radius, and aggregation number (the average number of monomers per micelle). The physical and chemical characteristics of a detergent determine micelle size and shape as well as the size and shape of the detergent layer on a protein. Detergent monomers are often assumed to form relatively uniform surfaces in micelles and in PDCs. This misconception arises from our simplistic cartoons of spherical micelles, wherein the hydrophobic tails, in a trans configuration, are shown extending toward the center of the micelle (Fig.2a). This geometrically impossible picture (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 9Tanford C. The Hydrophobic Effect. John Wiley & Sons, Inc., New York1980Google Scholar) obscures some important insights into how the size, shape, and behavior of a micelle (or a PDC) are dependent on detergent packing. More realistic pictures of a detergent micelle (Fig.2, b and c) have the hydrophobic tails packing in a much more disorganized but compact fashion (17Bogusz S. Venable R.M. Pastor R.W. J. Phys. Chem. B. 2000; 104: 5462-5470Crossref Scopus (135) Google Scholar, 18Tieleman D.P. van der Spoel D. Berendsen H.J.C. J. Phys. Chem. B. 2000; 104: 6380-6388Crossref Scopus (263) Google Scholar). Two consequences of micelle structure are now clearly evident: 1) the micelle surface is quite rough and heterogeneous in character and 2) not all hydrophobic tails are buried or point toward the center of the micelle. Hence, micelle radii are about 10–30% smaller than the fully extended length of the detergent monomer (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar), and many of the hydrophobic tails have considerable contact with water and solutes. Moreover, molecular dynamics studies (17Bogusz S. Venable R.M. Pastor R.W. J. Phys. Chem. B. 2000; 104: 5462-5470Crossref Scopus (135) Google Scholar, 18Tieleman D.P. van der Spoel D. Berendsen H.J.C. J. Phys. Chem. B. 2000; 104: 6380-6388Crossref Scopus (263) Google Scholar) also show that micelle shape is very dependent on aggregation number (Fig. 2, b and c) and that the concept of a “spherical” micelle really denotes only an average shape. The concept of a compact, disordered micelle clearly suggests that monomer packing defects could radically affect the size, shape, and behavior of micelles. As lipids, other detergents, or amphipathic solutes are incorporated into the micelles of a pure detergent to form mixed micelles, packing defects may be introduced or, on the other the detergents in a are to be well and the of detergents to or some membrane proteins arises from the packing of detergent monomers on the surface of the protein. misconception is that micelles are structures of uniform shape. The is often applied to to a uniform size and shape of a of detergents, is to be of in the size and shape Chem. 1979; Scopus Google Scholar). The experimental suggests that micelles are quite and micellar with the solvent (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar, M.J. K. Q. D. M. Biochim. Biophys. Acta. 1999; PubMed Scopus Google Scholar, C. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). of detergents can exhibit in micellar they can and (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 11Wennerström H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar, S. Venable R.M. Pastor R.W. J. Phys. Chem. B. 2000; 104: 5462-5470Crossref Scopus (135) Google Scholar, 18Tieleman D.P. van der Spoel D. Berendsen H.J.C. J. Phys. Chem. B. 2000; 104: 6380-6388Crossref Scopus (263) Google Scholar). some detergents, in micelle aggregation size, and shape may as the detergent concentration Wennerström H. Lindman B. J. Phys. Chem. 1983; Scopus Google Scholar, M. J. Phys. Chem. 1983; Scopus Google Scholar). in micelle shape, from spherical to or with many pure detergents Wennerström H. Lindman B. J. Phys. Chem. 1983; Scopus Google Scholar, M. J. Phys. Chem. 1983; Scopus Google Scholar) but may be more common when a detergent is mixed with or protein Levy D. J.L. G. J.L. Biophys. J. PubMed Scopus Google Scholar). and are only two of many phase that surfactant solutions may exhibit (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar). of detergent behavior in aqueous solutions are generally simple for the detergents with tails of (Fig. and detergents with tails of or to exhibit much more complex phase (Fig. some phase micellar to form with properties (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar). common detergent phenomenon is called the point (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar), a detergent solution The phase into two solutions one and the other The between the detergent phase and the of the two (Fig. is called a consolute (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar). C. J. Chem. PubMed Google Scholar) that this phase phenomenon could be for membrane protein and the technique of detergent phase is used Biochim. Biophys. Acta. 2000; PubMed Scopus Google Scholar). The phase by a surfactant are by its monomer structure as well as its chemistry (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar), its or for in the solvent can also the nature of surfactant aggregation (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, K. PubMed Scopus Google Scholar). The of or polar solutes to a detergent solution can radically the phase behavior of a detergent to well the relatively high detergent with the pure detergents (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, 16Mitchell D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar). The point phase is a problem membrane protein (2Garavito R.M. Markovic-Housley Z. Jenkins J.A. J. Crystal Growth. 1986; 76: 701-709Crossref Scopus (70) Google Scholar, 3Garavito R.M. Picot D. Loll P.J. J. Bioenerg. Biomembr. 1995; 28: 13-27Crossref Scopus (108) Google Scholar, 4Kühlbrandt W. Q. Rev. Biophys. 1988; 21: 429-477Crossref PubMed Scopus (139) Google Scholar) and is by a number of detergent type, and the detergents a lower consolute (Fig. As the micelles aggregate into (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, M. J. Phys. Chem. 1983; Scopus Google Scholar) these phase to form a new The of also the to lower (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, K. PubMed Scopus Google Scholar). In the of to solutions of detergents, such as β-d-octyl glucoside and an upper consolute to (Fig. The is that solution and affect not only the basic detergent phenomenon we rely on but also whether other detergent or What understanding surfactant phase important to membrane is that the use of detergents with membrane proteins to from protein to to a membrane protein will be influenced by and as well as with only detergents and lipids, is that mixed not solutions of the pure (10Rosen M.J. Surfactants and Interfacial Phenomena. John Wiley & Sons, Inc., New York1978Google H. Lindman B. Phys. Reports. 1979; 52: 1-86Crossref Scopus (535) Google Scholar). Hence, in micelle shape and size, CMC, and phase behavior can all and they are not for simple solutions two detergents. The of a membrane protein to the The and packing of the detergent monomers to the protein will affect the behavior and of the detergent This may in protein and protein detergent and protein from a will impact the (13Haneskog L. Andersson L. Brekkan E. Englund A.K. Kameyama K. Liljas L. Greijer E. Fischbarg J. Lundahl P. Biochim. Biophys. Acta. 1996; 1282: 39-47Crossref PubMed Scopus (20) Google Scholar, 14le Maire M. Kwee S. Andersen J. Møller J. Eur. J. Biochem. 1983; 129: 525-532Crossref PubMed Scopus (67) Google Maire M. Biophys. J. PubMed Scopus Google Scholar), characterization (13Haneskog L. Andersson L. Brekkan E. Englund A.K. Kameyama K. Liljas L. Greijer E. Fischbarg J. Lundahl P. Biochim. Biophys. Acta. 1996; 1282: 39-47Crossref PubMed Scopus (20) Google Scholar, 15Marone P.A. Thiyagarajan P. Wagner A.M. Tiede D.M. J. Crystal Growth. 1999; 207: 214-225Crossref Scopus (23) Google Scholar, C. J. M. J. Loll P.J. 2000; PubMed Scopus Google Scholar), and (13Haneskog L. Andersson L. Brekkan E. Englund A.K. Kameyama K. Liljas L. Greijer E. Fischbarg J. Lundahl P. Biochim. Biophys. Acta. 1996; 1282: 39-47Crossref PubMed Scopus (20) Google Scholar, Methods Enzymol. PubMed Scopus Google Scholar) of membrane proteins. When the added of other solvent in experimental conditions may to detergent not from the pure detergent behavior the and structure of is then important to membrane protein an on simple, R.M. Picot D. Loll P.J. J. Bioenerg. Biomembr. 1995; 28: 13-27Crossref Scopus (108) Google Scholar, 4Kühlbrandt W. Q. Rev. Biophys. 1988; 21: 429-477Crossref PubMed Scopus (139) Google Scholar), detergents that spherical micelles (8Zulauf M. Michel H. Crystallization of Membrane Proteins. CRC Press, Inc., Boca Raton, FL1991: 54-71Google Scholar, P.A. M. T. W. 1988; Scopus Google Scholar) to the shape, size, and behavior of the that phase an enormous impact on phase behavior could R.M. Methods Enzymol. 1986; PubMed Scopus Google Scholar) and protein H. J. PubMed Google Scholar). However, in many often as conditions approached an upper or lower consolute phase R.M. Picot D. Loll P.J. J. Bioenerg. Biomembr. 1995; 28: 13-27Crossref Scopus (108) Google Scholar). much has on understanding the between phase behavior of the and P.A. Thiyagarajan P. Wagner A.M. Tiede D.M. J. Crystal Growth. 1999; 207: 214-225Crossref Scopus (23) Google Scholar, C. J. M. J. Loll P.J. 2000; PubMed Scopus Google Scholar), as well as how the characteristics of the can be by detergents (2Garavito R.M. Markovic-Housley Z. Jenkins J.A. J. Crystal Growth. 1986; 76: 701-709Crossref Scopus (70) Google Scholar, 3Garavito R.M. Picot D. Loll P.J. J. Bioenerg. Biomembr. 1995; 28: 13-27Crossref Scopus (108) Google Scholar, P.A. M. T. W. 1988; Scopus Google Scholar, R.M. Methods Enzymol. 1986; PubMed Scopus Google Scholar) and the of P.A. Thiyagarajan P. Wagner A.M. Tiede D.M. J. Crystal Growth. 1999; 207: 214-225Crossref Scopus (23) Google Scholar, P. Tiede D.M. J. Phys. Chem. Scopus Google Scholar, P.A. J. T. W. PubMed Scopus Google Scholar). The characterization of membrane protein by and E. R.M. Zulauf M. P.A. 1995; PubMed Scopus Google Scholar, S. E. J. G. T. P.A. PubMed Scopus Google Scholar, M. B. A. PubMed Scopus Google Scholar, M. A. Michel H. J. D. Scopus Google Scholar) has a of information about the shape and structure of a the structures of in detergents and forms some aspects about detergent behavior. et al. E. R.M. Zulauf M. P.A. 1995; PubMed Scopus Google Scholar) the form of or the as a complex in et al. E. R.M. Zulauf M. P.A. 1995; PubMed Scopus Google the detergent layer as a and about the protein. In the complex a of the detergent with its in et al. E. R.M. Zulauf M. P.A. 1995; PubMed Scopus Google When et S. E. J. G. T. P.A. PubMed Scopus Google Scholar) the form of et S. E. J. G. T. P.A. PubMed Scopus Google the detergent about each with its to create a detergent the detergents that spherical or micelles can be to form more complex structures Moreover, are often an integral of the structure in membrane protein detergent and structure a in membrane protein and could more surfactants serve the and this question and with a of crystallizing membrane proteins S. A. 1996; PubMed Scopus Google Scholar, P. A. E. 1999; 457: PubMed Scopus Google Scholar). In essence, a surfactant phase with a more structure be used to membrane proteins into an that for and The surfactant by D.J. Tiddy G.J.T. Waring L. Bostock T. McDonald M.P. J. Chem. Soc. Faraday Trans. 1983; 79: 975-1000Crossref Google Scholar, J. H. M. J. Phys. 1996; Scopus Google Scholar) for this as of solvent and surfactant the phase and can with a solvent membrane added can into the the solvent the manipulation of the aqueous to Although many of the by and are not their technique the high resolution structure of H. P. A. C. E. 1999; PubMed Scopus Google Scholar, H. B. J. 1999; PubMed Scopus Google Scholar) and M. H. D. 2000; PubMed Scopus Google Scholar). The structure of from the phase above H. P. A. C. E. 1999; PubMed Scopus Google Scholar, H. B. J. 1999; PubMed Scopus Google Scholar) a a layer of lipid molecules on the protein The nature of the lipids, from the native and their in the and of the protein (Fig. specific and well Over the studies have that membrane lipids are the surface of integral membrane proteins P.J. D. Biophys. J. PubMed Scopus Google Scholar), a and by D. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). The of this of lipid has much but for many the has as a hydrophobic complex in its properties Rev. Biophys. 1999; 28: PubMed Scopus Google Scholar) also the in this by al. S. K. J. Chem. PubMed Scopus Google the of high resolution structures of membrane proteins, the of lipid molecules now to be a than an Moreover, these complexes of membrane proteins and lipid do not lipids, such as S. A. 1999; PubMed Scopus Google Scholar) or lipids H. B. J. 1999; PubMed Scopus Google Scholar), but also more common The structure of resolution and molecules per monomer T. H. E. T. H. K. S. 1996; PubMed Scopus Google Scholar). At resolution molecules, have which are only a of the lipids with that have by D. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). recent that lipid may membrane proteins assume more stable and Hence, many detergents may with of some native lipid P. G. Chem. Phys. 1995; PubMed Scopus Google Scholar). In complete lipid that a detergent be to successfully for not lipid used in structure A. PubMed Scopus Google Scholar, D.M. PubMed Scopus Google the of some may be critical for The structures of K. T. T. H. T. M. M. 2000; PubMed Scopus Google Scholar) and the C. M. H. H. 2000; PubMed Scopus Google Scholar) this In the of a detergent T. K. J. 2000; PubMed Scopus Google Scholar), the of the involved of lipid C. M. H. H. 2000; PubMed Scopus Google Scholar). The of these is in of how we the use of detergents in As the complete of lipid to an for or to self-association into aggregates Maire M. Biophys. J. PubMed Scopus Google Scholar), which is often by However, complete of lipid from many membrane proteins is and is often to structure and function (13Haneskog L. Andersson L. Brekkan E. Englund A.K. Kameyama K. Liljas L. Greijer E. Fischbarg J. Lundahl P. Biochim. Biophys. Acta. 1996; 1282: 39-47Crossref PubMed Scopus (20) Google Scholar, B. P. Eur. J. Biochem. PubMed Scopus Google Scholar, S. S. B. P. Maire M. J. Chem. PubMed Google Scholar). when forms can be in the of membrane proteins may be influenced by the of studies M. S. S. H. A. H. Biochim. Biophys. Acta. PubMed Scopus Google Scholar) clearly as native lipid conditions and detergents that can PubMed Scopus Google Scholar, S. 1983; PubMed Scopus Google Scholar) may that are not in B. P. Eur. J. Biochem. PubMed Scopus Google Scholar, J. K. S. B. Chem. PubMed Scopus Google Scholar, A. J. 2000; PubMed Scopus Google Scholar). Hence, complete may not be the when with the of structure Maire M. Biophys. J. PubMed Scopus Google Scholar). The critical of detergents in all aspects of membrane protein biochemistry be fully in the context of this As the behavior of detergents clearly membrane protein and as well as (1Rigaud J.L. Pitard B. Levy D. Biochim. Biophys. Acta. 1995; 1231: 223-246Crossref PubMed Scopus (409) Google Scholar), which not However, a can be that to all systems. The nature of the solubilization detergent is an important in the size and properties of the PDCs. Moreover, the lipid in the protein is a critical but often we to a new is not and of specific may be the more for and studies of membrane proteins. et al. P. G. Chem. Phys. 1995; PubMed Scopus Google Scholar) that detergents kinds and of lipids from the with often with significant in of the protein. studies may be for the successful of many membrane proteins.