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Review
. 2021 Jul 7;11(7):1771.
doi: 10.3390/nano11071771.

Current Developments in Native Nanometric Discoidal Membrane Bilayer Formed by Amphipathic Polymers

Mansoore Esmaili  1 , Mohamed A Eldeeb  2   3 , Ali Akbar Moosavi-Movahedi  4
Affiliations
Review

Current Developments in Native Nanometric Discoidal Membrane Bilayer Formed by Amphipathic Polymers

Mansoore Esmaili et al. Nanomaterials (Basel). .

Abstract

Unlike cytosolic proteins, membrane proteins (MPs) are embedded within the plasma membrane and the lipid bilayer of intracellular organelles. MPs serve in various cellular processes and account for over 65% of the current drug targets. The development of membrane mimetic systems such as bicelles, short synthetic polymers or amphipols, and membrane scaffold proteins (MSP)-based nanodiscs has facilitated the accommodation of synthetic lipids to stabilize MPs, yet the preparation of these membrane mimetics remains detergent-dependent. Bio-inspired synthetic polymers present an invaluable tool for excision and liberation of superstructures of MPs and their surrounding annular lipid bilayer in the nanometric discoidal assemblies. In this article, we discuss the significance of self-assembling process in design of biomimetic systems, review development of multiple series of amphipathic polymers and the significance of these polymeric "belts" in biomedical research in particular in unraveling the structures, dynamics and functions of several high-value membrane protein targets.

Keywords: amphipathic; heteropolymers; lipid bilayer; membrane proteins; self-assembly; synthetic biology.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Schematic view of diverse biopolymers in cells, and their resemblance to chemically synthesized polymers that have been shown broad utilities in biomedical research. During the synthetic process of homo ad heteropolymers, optimizing the sequence, length and shape (linear vs. circular), backbone flexibility, stereochemistry, and homogeneity are crucially difficult to manage.
Figure 2
Figure 2
Random copolymerization of building blocks (cyan and pink circles) (A) via random chain growth and (B) step growth polymerization mechanisms. Asterisks represent the radical atoms. Initiator and terminator are, respectively, shown as in green and red.
Figure 3
Figure 3
General arrangement of comonomers in heretopolymers lead to seven major classes of amphiphilic polymers.
Figure 4
Figure 4
Styrene-maleic acid copolymers were efficient vehicles for encapsulation of hydrophobic drug-like molecules such as doxorubicin, zinc protoporphyrin, pirarubicin.
Figure 5
Figure 5
Adsorption, and hydrophobic interaction of styrene moieties (or their hydrophophobic counterparts in other membrane solubilizing polymers such as DIBMA) with acyl chains of phospholipids in lipid bilayer leads to fragmentation the membrane and formation of nanoscale entities called polymer-lipid particles (i.e., SMALP, DIBMALP, etc.).
Figure 6
Figure 6
(A) SMA polymers form pores in supported lipid bilayer (shown in blue). The same process has been observed in the cells, making them permeable to water and small water-soluble fluorescent molecules (B) Schematic view of how encapsulation event perturbs the membrane and leads to membrane fragmentation and formation of discs.
Figure 7
Figure 7
Top and side views of high-resolution cryo-EM structures of (A) trimeric AcrB with lipid molecules in yellow (PDB 6BAJ, EMD 7074), (B) side views of ACIII photosystem complex (EMD 7286 and 7448), (C) dimeric KimA (PDB 6S3K), (D) heptameric Ynal (PDB 6RLD, EMD 4990), (E) pentameric GlyR (PDB 6PLZ), (F) symmetric trimer of Plant BdSLAC1 (PDB 7EN0; EMD-31197). (G) The in meso crystal structure of trimeric rhodopsin bound to monoolein after solubilization with SMA. The structure contains three subunits of the trimer (green, blue, red) and nine monoolein lipids (yellow) within the interfaces (PDB 5ITC).
Figure 7
Figure 7
Top and side views of high-resolution cryo-EM structures of (A) trimeric AcrB with lipid molecules in yellow (PDB 6BAJ, EMD 7074), (B) side views of ACIII photosystem complex (EMD 7286 and 7448), (C) dimeric KimA (PDB 6S3K), (D) heptameric Ynal (PDB 6RLD, EMD 4990), (E) pentameric GlyR (PDB 6PLZ), (F) symmetric trimer of Plant BdSLAC1 (PDB 7EN0; EMD-31197). (G) The in meso crystal structure of trimeric rhodopsin bound to monoolein after solubilization with SMA. The structure contains three subunits of the trimer (green, blue, red) and nine monoolein lipids (yellow) within the interfaces (PDB 5ITC).
Figure 7
Figure 7
Top and side views of high-resolution cryo-EM structures of (A) trimeric AcrB with lipid molecules in yellow (PDB 6BAJ, EMD 7074), (B) side views of ACIII photosystem complex (EMD 7286 and 7448), (C) dimeric KimA (PDB 6S3K), (D) heptameric Ynal (PDB 6RLD, EMD 4990), (E) pentameric GlyR (PDB 6PLZ), (F) symmetric trimer of Plant BdSLAC1 (PDB 7EN0; EMD-31197). (G) The in meso crystal structure of trimeric rhodopsin bound to monoolein after solubilization with SMA. The structure contains three subunits of the trimer (green, blue, red) and nine monoolein lipids (yellow) within the interfaces (PDB 5ITC).
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