Fake It ‘Till You Make It—The Pursuit of Suitable Membrane Mimetics for Membrane Protein Biophysics

Thoma, Johannes; Burmann, Björn M.

doi:10.3390/ijms22010050

Cited by 24 publications

(36 citation statements)

References 245 publications

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“…In addition, paramagnetic ions can be added to the lipid mixtures, so the resulting bicelles can align in an external magnetic field, aiding magnetic resonance studies on IMPs [155,156]. Notably, the presence of detergent-like short-chain lipids and a bilayer size is insufficient to provide membrane-like lateral pressure and may perturb the structure and dynamics of bicelle-residing IMPs [54,69,157]. Another disadvantage of conventional bicelles is that their size and geometry depend on the total lipid concentration in the solution; therefore, any dilution changes the system properties.…”

Section: Bicelles In Studies Of Integral Membrane Proteins 221 General Properties Of Bicellesmentioning

confidence: 99%

“…The development of lipid membrane mimetics to make IMPs amenable for isolation, purification, and in vitro characterization has a long history. Generally, a membrane mimetic should reproduce the lipid bilayer properties, or at least recreate the hydrophobic core environment of a lipid bilayer in its most fundamental form [ 54 , 56 ]. Although detergents have been the most widely used substitute for the membrane environment, in the recent decades a great deal of effort has been invested to expand the diversity of membrane mimetics and to use more lipid bilayer-like structures, which together with the incorporated proteins have high solubility and stability.…”

Section: An Overview Of the Most Widely Used Lipid Membrane Mimetics And Their Applications In Functional And Structural Studies Of Integmentioning

confidence: 99%

“…Another serious issue is identifying and developing appropriate membrane protein hosts, i.e., lipid membrane-like mimetics, to which IMPs are transferred from the native membranes where they are expressed, or from inclusion bodies in the case of eukaryotic or viral proteins produced in E. coli. [49] This is needed for further purification and in vitro functional and structural studies [50][51][52][53][54]. In general, IMPs are difficult to solubilize away from their native environment in the cell membrane due to their hydrophobic regions [55].…”

Section: Introductionmentioning

confidence: 99%

“…In general, IMPs are difficult to solubilize away from their native environment in the cell membrane due to their hydrophobic regions [ 55 ]. Also, removing these proteins from their native cellular form sometimes results in evident functional and structural implications [ 54 ]. Thus, selecting a suitable membrane mimetic for each particular protein is critical for obtaining samples of functional proteins for in vitro studies on active or purposely inhibited protein states.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

et al. 2021

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Integral membrane proteins (IMPs) fulfill important physiological functions by providing cell–environment, cell–cell and virus–host communication; nutrients intake; export of toxic compounds out of cells; and more. However, some IMPs have obliterated functions due to polypeptide mutations, modifications in membrane properties and/or other environmental factors—resulting in damaged binding to ligands and the adoption of non-physiological conformations that prevent the protein from returning to its physiological state. Thus, elucidating IMPs’ mechanisms of function and malfunction at the molecular level is important for enhancing our understanding of cell and organism physiology. This understanding also helps pharmaceutical developments for restoring or inhibiting protein activity. To this end, in vitro studies provide invaluable information about IMPs’ structure and the relation between structural dynamics and function. Typically, these studies are conducted on transferred from native membranes to membrane-mimicking nano-platforms (membrane mimetics) purified IMPs. Here, we review the most widely used membrane mimetics in structural and functional studies of IMPs. These membrane mimetics are detergents, liposomes, bicelles, nanodiscs/Lipodisqs, amphipols, and lipidic cubic phases. We also discuss the protocols for IMPs reconstitution in membrane mimetics as well as the applicability of these membrane mimetic-IMP complexes in studies via a variety of biochemical, biophysical, and structural biology techniques.

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Section: Bicelles In Studies Of Integral Membrane Proteins 221 General Properties Of Bicellesmentioning

confidence: 99%

Section: An Overview Of the Most Widely Used Lipid Membrane Mimetics And Their Applications In Functional And Structural Studies Of Integmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

et al. 2021

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“…The use of styrene maleic-acid lipid particles (SMALPs)—also called ‘native nanodiscs’ or lipodisqs—is also popular since it retains the native lipid composition of the IMP under study [ 15 ]. The pros and cons of each of these mimics have been reviewed elsewhere [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Assessing the Role of Lipids in the Molecular Mechanism of Membrane Proteins

Jodaitis

Oene

Martens

2021

IJMS

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Membrane proteins have evolved to work optimally within the complex environment of the biological membrane. Consequently, interactions with surrounding lipids are part of their molecular mechanism. Yet, the identification of lipid–protein interactions and the assessment of their molecular role is an experimental challenge. Recently, biophysical approaches have emerged that are compatible with the study of membrane proteins in an environment closer to the biological membrane. These novel approaches revealed specific mechanisms of regulation of membrane protein function. Lipids have been shown to play a role in oligomerization, conformational transitions or allosteric coupling. In this review, we summarize the recent biophysical approaches, or combination thereof, that allow to decipher the role of lipid–protein interactions in the mechanism of membrane proteins.

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Tunable Composition of Mixed Self‐Assembled Shell‐by‐Shell Structures on Nanoparticle Surfaces

Eigen

Stiegler

Gradl

et al. 2022

Adv Materials Inter

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of the individual molecules has a decisive influence on the final properties of the resulting suprastructure. In micelles, this can be the size and shape, for vesicles, the diffusion speed through the molecular bilayer, or for self-assembled monolayers (SAMs) the packing density and crystallinity. [1][2][3][4] Properties of such assemblies can be either modified by tuning the individual molecules or by a smart combination of multiple building blocks. [5][6][7][8][9][10][11][12][13] This concept is proven by nature as a highly reliable method to create, for example, cell membranes, which consist of hundreds of different molecules, even for the simplest organisms resulting in remarkably high functionality. [14,15] Among many other tasks, those molecules control the stability, the salt content in cells, the oxygen and nutrient uptake, and the size of these structures. [15] The exact selection of molecule types and stoichiometric composition of membranes play a decisive role in the functioning of the cells. Most prominent examples are amphiphiles that consist of two parts of different polarities, thus making them soluble in orthogonal solvents.All corresponding suprastructures are based on weak hydrophobic interactions as well as intermolecular recognition motifs such as stereo complexation, H-bonding, ionic interactions, etc. [16] But even in simple artificial micelles and vesicles (compared to biological systems), competing forces between two or more molecules can either lead to synergetic effects or segregation of the involved molecules into multiple structures with heterogeneous composition. [17,18] In particular for the combination of highly orthogonal amphiphiles bearing fluorophilic and lipophilic (alkyl-chained) residues, there are only a few examples of synergetic mixtures known. [18,19] However, such orthogonally chained molecules tend to self-assemble to mixed SAMs if they exhibit strong covalent binding anchor groups such as phosphonic acids. The covalent binding drives the self-assembly on, for example, oxide surfaces and prevent the individual molecules from segregating into multiple phases, which allows the formation of SAMs in any stoichiometric mixing ratio. [20] Based on such SAMs, vesicle-like structures (see Scheme 1) can be formed with nanoparticles as template by building up a second layer through non-covalent interactions to a shell-by-shell (SbS) system. [21][22][23][24][25][26] Such unique systems provide the opportunity to switch the polarity of core-shell nanoparticles for adjusted processing, [21] to prepare model bilayers The formation of mixed shell-by-shell (SbS) systems with tunable shell compositions is demonstrated by using molecular self-assembly driven by chemical recognition motifs. Aluminum oxide nanoparticles (AlOx-NPs) act as template surface for a self-assembled monolayer (SAM) of either partially fluorinated fluoroalkyl or alkyl chained phosphonic acid derivatives or defined stoichiometric mixtures of those. By providing an equimolar mixture of corresponding fluoroalkyl and a...

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Fake It ‘Till You Make It—The Pursuit of Suitable Membrane Mimetics for Membrane Protein Biophysics

Cited by 24 publications

References 245 publications

Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

Assessing the Role of Lipids in the Molecular Mechanism of Membrane Proteins

Tunable Composition of Mixed Self‐Assembled Shell‐by‐Shell Structures on Nanoparticle Surfaces

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