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1. Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase

   https://doi.org/10.3390/sym13081441  

   Frewein, Moritz P. ; Doktorova, Milka ; Heberle, Frederick A. ; Scott, Haden L. ; Semeraro, Enrico F. ; Porcar, Lionel ; Pabst, Georg ( August 2021 , Symmetry)

   null (Ed.)

   We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the sn1-chain penetrate deeper into the opposing leaflet by half a CH2 group. That is, penetration-depth differences due to the ester-linked hydrocarbons at the glycerol backbone, previously reported for gel phase structures, also extend to the more relevant physiological fluid phase, but are significantly reduced. Moreover, milk sphingomyelin was found to follow the same linear relationship suggesting a similar tilt of the sphingosine backbone. Complementarily performed molecular dynamics simulations revealed that there is always a part of the lipid tails bending back, even if there is a high interdigitation with the opposing chains. The extent of this back-bending was similar to that in chain symmetric bilayers. For both cases of adaptation to chain length mismatch, chain-asymmetry has a large impact on hydrocarbon chain ordering, inducing disorder in the longer of the two hydrocarbons. 

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2. Transverse lipid organization dictates bending fluctuations in model plasma membranes

   https://doi.org/10.1039/C9NR07977G  

   Rickeard, Brett W. ; Nguyen, Michael H. ; DiPasquale, Mitchell ; Yip, Caesar G. ; Baker, Hamilton ; Heberle, Frederick A. ; Zuo, Xiaobing ; Kelley, Elizabeth G. ; Nagao, Michihiro ; Marquardt, Drew ( January 2020 , Nanoscale)

   Membrane undulations play a vital role in many biological processes, including the regulation of membrane protein activity. The asymmetric lipid composition of most biological membranes complicates theoretical description of these bending fluctuations, yet experimental data that would inform any such a theory is scarce. Here, we used neutron spin-echo (NSE) spectroscopy to measure the bending fluctuations of large unilamellar vesicles (LUV) having an asymmetric transbilayer distribution of high- and low-melting lipids. The asymmetric vesicles were prepared using cyclodextrin-mediated lipid exchange, and were composed of an outer leaflet enriched in egg sphingomyelin (ESM) and an inner leaflet enriched in 1-palmitoyl-2-oleoyl-phosphoethanolamine (POPE), which have main transition temperatures of 37 °C and 25 °C, respectively. The overall membrane bending rigidity was measured at three temperatures: 15 °C, where both lipids are in a gel state; 45 °C, where both lipids are in a fluid state; and 30 °C, where there is gel-fluid co-existence. Remarkably, the dynamics for the fluid asymmetric LUVs (aLUVs) at 30 °C and 45 °C do not follow trends predicted by their symmetric counterparts. At 30 °C, compositional asymmetry suppressed the bending fluctuations, with the asymmetric bilayer exhibiting a larger bending modulus than that of symmetric bilayers corresponding to either the outer or inner leaflet. We conclude that the compositional asymmetry and leaflet coupling influence the internal dissipation within the bilayer and result in membrane properties that cannot be directly predicted from corresponding symmetric bilayers. 

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3. Quantitative relationship between cholesterol distribution and ordering of lipids in asymmetric lipid bilayers

   https://doi.org/10.1039/d0sm01709d  

   Aghaaminiha, Mohammadreza ; Farnoud, Amir M. ; Sharma, Sumit ( March 2021 , Soft Matter)

   null (Ed.)

   The plasma membrane of eukaryotic cells is known to be compositionally asymmetric. Certain phospholipids, such as sphingomyelin and phosphatidylcholine species, are predominantly localized in the outer leaflet, while phosphatidylethanolamine and phosphatidylserine species primarily reside in the inner leaflet. While phospholipid asymmetry between the membrane leaflets is well established, there is no consensus about cholesterol distribution between the two leaflets. We have performed a systematic study, via molecular simulations, of how the spatial distribution of cholesterol molecules in different “asymmetric” lipid bilayers are affected by the lipids’ backbone, head-type, unsaturation, and chain-length by considering an asymmetric bilayer mimicking the plasma membrane lipids of red blood cells, as well as seventeen other asymmetric bilayers comprising of different lipid types. Our results reveal that the distribution of cholesterol in the leaflets is solely a function of the extent of ordering of the lipids within the leaflets. The ratio of the amount of cholesterol matches the ratio of lipid order in the two leaflets, thus providing a quantitative relationship between the two. These results are understood by the observation that asymmetric bilayers with equimolar amount of lipids in the two leaflets develop tensile and compressive stresses due to differences in the extent of lipid order. These stresses are alleviated by the transfer of cholesterol from the leaflet in compressive stress to the one in tensile stress. These findings are important in understanding the biology of the cell membrane, especially with regard to the composition of the membrane leaflets. 

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4. Facile polymerization in a bicellar template to produce polymer nano-rings

   https://doi.org/10.1016/j.jcis.2022.09.141  

   Liu, Chung-Hao ; Cheu, Catherine ; Barker, John G. ; Yang, Lin ; Nieh, Mu-Ping ( January 2023 , Journal of Colloid and Interface Science)

   Hypothesis: A well-defined discoidal bicelle composed of three lipids, specifically zwitterionic long-chain 1,2 dipalmitoyl phosphocholine (DPPC) and short-chain 1,2 dihexanoyl phosphocholine (DHPC) doped with anionic 1,2 dipalmitoyl phosphoglycerol (DPPG) provides a generalized template for the synthesis of hydrophobic polymer nano-rings. The lipid molar ratio of DPPC/DHPC/DPPG is 0.71/0.25/0.04. The detailed investigation and discussion were based on styrene but tested on three other vinyl monomers. Experiments: The structure of nano-rings is identified through the detailed analysis of small angle X-ray/ neutron scattering (SAXS and SANS) data and transmission electron micrographs (TEM), supported by the differential scanning calorimetric (DSC) data before and after polymerization. The investigation covers samples with a styrene-to-lipid ratio ranged varied from 1:50 to 1:10. Findings: The styrene monomers are initially located at both the discoidal planar (long-chain lipid rich) and rim (short-chain lipid rich) regions. During polymerization, they migrate to the more fluid rim regionsection. The formation mechanism involves the interplay of hydrophobic interaction, mismatched miscibility of polystyrene between the ordered and disordered phases, and crystallinity of the long lipid acyl chains. This facile synthesis is proven applicable for several hydrophobic monomers. The welldefined nano-rings greatly enhance the interfacial area and have the potential to be the building blocks for functional materials, if monomers are incorporated with desirable functions, for future applications. 

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5. Spontaneous bilayer wrapping of virus particles by a phospholipid Langmuir monolayer

   https://doi.org/10.1140/epje/s10189-023-00366-8  

   Torres-Salgado, J. F. ; Villagrana-Escareño, M. V. ; Duran-Meza, A. L. ; Segovia-Gonzalez, X. F. ; Cadena-Nava, R. D. ; Gelbart, W. M. ; Knobler, C. M. ; Ruiz-García, J. ( December 2023 , The European Physical Journal E)

   We report here the spontaneous formation of lipid-bilayer-wrapped virus particles, following the injection of “naked” virus particles into the subphase of a Langmuir trough with a liquid monolayer of lipids at its air–water interface. The virus particles are those of the well-studied cowpea chlorotic mottle virus, CCMV, which are negatively charged at the pH 6 of the subphase; the lipids are a 9:1 mix of neutral DMPC and cationic CTAB molecules. Before adding CCMV particles to the subphase we establish the mixed lipid monolayer in its liquid-expanded state at a fixed pressure (17.5 mN/m) and average area-per-molecule of (41Ų). Keeping the total area fixed, the surface pressure is observed to decrease at about 15 h after adding the virus particles in the subphase; by 37 h it has dropped to zero, corresponding to essentially all the lipid molecules having been removed from the air–water interface. By collecting particles from the subphase and measuring their sizes by atomic force microscopy, we show that the virus particles have been wrapped by lipid bilayers (or by two lipid bilayers). These results can be understood in terms of thermal fluctuations and electrostatic interactions driving the wrapping of the anionic virus particles by the cationic lipids.

   Graphical Abstract

    

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