Symmetric and Asymmetric Cellular Membranes

A special issue of Symmetry (ISSN 2073-8994). This special issue belongs to the section "Chemistry: Symmetry/Asymmetry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19086

Special Issue Editor


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Guest Editor
1. Department of Chemistry & Biochemistry, University of Windsor, ON, Canada
2. Department of Physics, University of Windsor, ON, Canada
Interests: biophysics; neutron scattering; membranes

Special Issue Information

Dear Colleagues,

The structure and function of cellular membranes remains among the most challenging areas in both the life and physical sciences. Cellular membranes are complex assemblies that play an active role in many cellular functions. Many of these membrane functions rely on a diverse scaffold of lipids, sterols, proteins and carbohydrates; all of which organize both in the plane of the membrane (laterally) and across the leaflets of the membrane (transversely). Of recent years, the investigation of trans-membrane symmetry (or lack thereof) has become a topic of widespread interest. Probing symmetries within cellular membranes has proven a necessity due to the ubiquity of trans-bilayer asymmetry in natural cell membranes. Understanding the membrane -- its structure, its dynamic behavior and its function – relies on cutting edge experimental techniques and the creativity membrane researchers from all disciplines.

We welcome contributions on any area or aspect (including experimental approaches) of symmetry/asymmetry of cellular membranes.

Dr. Drew Marquardt
Guest Editor

Manuscript Submission Information

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Keywords

  • cell membrane
  • lipid asymmetry
  • protein asymmetry
  • ion asymmetry
  • eukaryotic membranes
  • prokaryotic membranes

Published Papers (5 papers)

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Research

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12 pages, 698 KiB  
Article
Nanoscale Bending Dynamics in Mixed-Chain Lipid Membranes
by Elizabeth G. Kelley, Moritz P. K. Frewein, Orsolya Czakkel and Michihiro Nagao
Symmetry 2023, 15(1), 191; https://doi.org/10.3390/sym15010191 - 9 Jan 2023
Cited by 2 | Viewed by 1568
Abstract
Lipids that have two tails of different lengths are found throughout biomembranes in nature, yet the effects of this asymmetry on the membrane properties are not well understood, especially when it comes to the membrane dynamics. Here we study the nanoscale bending fluctuations [...] Read more.
Lipids that have two tails of different lengths are found throughout biomembranes in nature, yet the effects of this asymmetry on the membrane properties are not well understood, especially when it comes to the membrane dynamics. Here we study the nanoscale bending fluctuations in model mixed-chain 14:0–18:0 PC (MSPC) and 18:0–14:0 PC (SMPC) lipid bilayers using neutron spin echo (NSE) spectroscopy. We find that despite the partial interdigitation that is known to persist in the fluid phase of these membranes, the collective fluctuations are enhanced on timescales of tens of nanoseconds, and the chain-asymmetric lipid bilayers are softer than an analogous chain-symmetric lipid bilayer with the same average number of carbons in the acyl tails, di-16:0 PC (DPPC). Quantitative comparison of the NSE results suggests that the enhanced bending fluctuations at the nanosecond timescales are consistent with experimental and computational studies that showed the compressibility moduli of chain-asymmetric lipid membranes are 20% to 40% lower than chain-symmetric lipid membranes. These studies add to growing evidence that the partial interdigitation in mixed-chain lipid membranes is highly dynamic in the fluid phase and impacts membrane dynamic processes from the molecular to mesoscopic length scales without significantly changing the bilayer thickness or area per lipid. Full article
(This article belongs to the Special Issue Symmetric and Asymmetric Cellular Membranes)
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25 pages, 19017 KiB  
Article
Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase
by Moritz P. K. Frewein, Milka Doktorova, Frederick A. Heberle, Haden L. Scott, Enrico F. Semeraro, Lionel Porcar and Georg Pabst
Symmetry 2021, 13(8), 1441; https://doi.org/10.3390/sym13081441 - 5 Aug 2021
Cited by 10 | Viewed by 2524
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Symmetric and Asymmetric Cellular Membranes)
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10 pages, 693 KiB  
Article
Pinocytosis as the Biological Mechanism That Protects Pgp Function in Multidrug Resistant Cancer Cells and in Blood–Brain Barrier Endothelial Cells
by Ziad Omran, Chloe Whitehouse, Majed Halwani, Mazin A. Zamzami, Othman A. Baothman and Cyril Rauch
Symmetry 2020, 12(8), 1221; https://doi.org/10.3390/sym12081221 - 25 Jul 2020
Cited by 4 | Viewed by 2141
Abstract
Cancer is the second leading cause of death worldwide. Chemotherapy has shown reasonable success in treating cancer. However, multidrug resistance (MDR), a phenomenon by which cancerous cells become resistant to a broad range of functionally and structurally unrelated chemotherapeutic agents, is a major [...] Read more.
Cancer is the second leading cause of death worldwide. Chemotherapy has shown reasonable success in treating cancer. However, multidrug resistance (MDR), a phenomenon by which cancerous cells become resistant to a broad range of functionally and structurally unrelated chemotherapeutic agents, is a major drawback in the effective use of chemotherapeutic agents in the clinic. Overexpression of P-glycoprotein (Pgp) is a major cause of MDR in cancer as it actively effluxes a wide range of structurally and chemically unrelated substrates, including chemotherapeutic agents. Interestingly, Pgp is also overexpressed in the endothelial cells of blood–brain barrier (BBB) restricting the entry of 98% small molecule drugs to the brain. The efficacy of Pgp is sensitive to any impairment of the membrane structure. A small increase of 2% in the membrane surface tension, which can be caused by a very low drug concentration, is enough to block the Pgp function. We demonstrate in this work by mathematical equations that the incorporation of drugs does increase the surface tension as expected, and the mechanism of endocytosis dissipates any increase in surface tension by augmenting the internalisation of membrane per unit of time, such that an increase in the surface tension of about 2% can be dissipated within only 4.5 s. Full article
(This article belongs to the Special Issue Symmetric and Asymmetric Cellular Membranes)
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Review

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21 pages, 11475 KiB  
Review
Model Membrane Systems Used to Study Plasma Membrane Lipid Asymmetry
by Haden L. Scott, Kristen B. Kennison, Thais A. Enoki, Milka Doktorova, Jacob J. Kinnun, Frederick A. Heberle and John Katsaras
Symmetry 2021, 13(8), 1356; https://doi.org/10.3390/sym13081356 - 26 Jul 2021
Cited by 21 | Viewed by 3837
Abstract
It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid–lipid and lipid–protein interactions. This is [...] Read more.
It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid–lipid and lipid–protein interactions. This is primarily due to the difficulty in preparing stable, asymmetric model membranes that are amenable to biophysical studies. However, in the last 20 years, efforts have been made in producing more biologically faithful model membranes. Here, we review several recently developed experimental and computational techniques for the robust generation of asymmetric model membranes and highlight a new and particularly promising technique to study membrane asymmetry. Full article
(This article belongs to the Special Issue Symmetric and Asymmetric Cellular Membranes)
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19 pages, 494 KiB  
Review
Simulated Breathing: Application of Molecular Dynamics Simulations to Pulmonary Lung Surfactant
by Maksymilian Dziura, Basel Mansour, Mitchell DiPasquale, P. Charukeshi Chandrasekera, James W. Gauld and Drew Marquardt
Symmetry 2021, 13(7), 1259; https://doi.org/10.3390/sym13071259 - 14 Jul 2021
Cited by 8 | Viewed by 7550
Abstract
In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, [...] Read more.
In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, down to the specific building blocks used, such as the various lipid and protein components. The lipid and protein composition varies across species and between individuals, but ultimately produces a PS monolayer with the same role. As such, the composition has been investigated for the ways in which it imposes function and confers peculiar biophysical characteristics to the system as a whole. Moreover, a couple of theories/models that are associated with the functions of PS have been addressed. Finally, molecular dynamic (MD) simulations of pulmonary surfactant have been emphasized to not only showcase various group’s findings, but also to demonstrate the validity and importance that MD simulations can have in future research exploring the PS monolayer system. Full article
(This article belongs to the Special Issue Symmetric and Asymmetric Cellular Membranes)
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