Recent Developments in Biophysical Studies of Cell Membranes

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 9949

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Guest Editor
Oak Ridge National Laboratory, Neutron Scattering Division, Oak Ridge, TN 37831, USA
Interests: membrane biophysics; model membranes; biomembranes; lipid bilayers; small-angle neutron scattering; peptide interactions with membranes
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Special Issue Information

Dear Colleagues,

A Special Issue on “Recent Developments in Biophysical Studies of Cell Membranes” is being prepared for the journal Biomolecules.

The cellular membrane continues to entice researchers to investigate its composition, structure, function and physical properties.  It is made of a diverse array of lipids, proteins and carbohydrates, which gives rise to a highly heterogenous structure that is vital for its function.  While considerable advances have been made in understanding the cellular membrane through creative applications of biophysical techniques, a great deal remains to be learned about them.  In this Special Issue, articles describing studies of cellular membranes, and model membranes, that have been performed using a variety of biophysical characterization techniques will be collected to highlight advances that have been made in understanding the complexity of cellular membranes and their constituents.  Reviews and original manuscripts presenting biophysical studies of cellular membranes, as well as model cell membranes, will be welcome contributions to the Special Issue.

Dr. William T. Heller
Guest Editor

Manuscript Submission Information

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Keywords

  • membrane biophysics
  • cell membranes
  • model cell membranes

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Published Papers (5 papers)

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Research

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16 pages, 6379 KiB  
Article
Transportan 10 Induces Perturbation and Pores Formation in Giant Plasma Membrane Vesicles Derived from Cancer Liver Cells
by Sara Anselmo, Giuseppe Sancataldo, Concetta Baiamonte, Giuseppe Pizzolanti and Valeria Vetri
Biomolecules 2023, 13(3), 492; https://doi.org/10.3390/biom13030492 - 07 Mar 2023
Cited by 2 | Viewed by 1555
Abstract
Continuous progress has been made in the development of new molecules for therapeutic purposes. This is driven by the need to address several challenges such as molecular instability and biocompatibility, difficulties in crossing the plasma membrane, and the development of host resistance. In [...] Read more.
Continuous progress has been made in the development of new molecules for therapeutic purposes. This is driven by the need to address several challenges such as molecular instability and biocompatibility, difficulties in crossing the plasma membrane, and the development of host resistance. In this context, cell-penetrating peptides (CPPs) constitute a promising tool for the development of new therapies due to their intrinsic ability to deliver therapeutic molecules to cells and tissues. These short peptides have gained increasing attention for applications in drug delivery as well as for their antimicrobial and anticancer activity but the general rules regulating the events involved in cellular uptake and in the following processes are still unclear. Here, we use fluorescence microscopy methods to analyze the interactions between the multifunctional peptide Transportan 10 (TP10) and the giant plasma membrane vesicles (GPMVs) derived from cancer cells. This aims to highlight the molecular mechanisms underlying functional interactions which bring its translocation across the membrane or cytotoxic mechanisms leading to membrane collapse and disruption. The Fluorescence Lifetime Imaging Microscopy (FLIM) method coupled with the phasor approach analysis proved to be the winning choice for following highly dynamic spatially heterogeneous events in real-time and highlighting aspects of such complex phenomena. Thanks to the presented approach, we were able to identify and monitor TP10 translocation into the lumen, internalization, and membrane-induced modifications depending on the peptide concentration regime. Full article
(This article belongs to the Special Issue Recent Developments in Biophysical Studies of Cell Membranes)
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12 pages, 2577 KiB  
Article
Phosphatidic Acid Accumulates at Areas of Curvature in Tubulated Lipid Bilayers and Liposomes
by Broderick L. Bills and Michelle K. Knowles
Biomolecules 2022, 12(11), 1707; https://doi.org/10.3390/biom12111707 - 17 Nov 2022
Cited by 3 | Viewed by 1782
Abstract
Phosphatidic acid (PA) is a signaling lipid that is produced enzymatically from phosphatidylcholine (PC), lysophosphatidic acid, or diacylglycerol. Compared to PC, PA lacks a choline moiety on the headgroup, making the headgroup smaller than that of PC and PA, and PA has a [...] Read more.
Phosphatidic acid (PA) is a signaling lipid that is produced enzymatically from phosphatidylcholine (PC), lysophosphatidic acid, or diacylglycerol. Compared to PC, PA lacks a choline moiety on the headgroup, making the headgroup smaller than that of PC and PA, and PA has a net negative charge. Unlike the cylindrical geometry of PC, PA, with its small headgroup relative to the two fatty acid tails, is proposed to support negatively curved membranes. Thus, PA is thought to play a role in a variety of biological processes that involve bending membranes, such as the formation of intraluminal vesicles in multivesicular bodies and membrane fusion. Using supported tubulated lipid bilayers (STuBs), the extent to which PA localizes to curved membranes was determined. STuBs were created via liposome deposition with varying concentrations of NaCl (500 mM to 1 M) on glass to form supported bilayers with connected tubules. The location of fluorescently labeled lipids relative to tubules was determined by imaging with total internal reflection or confocal fluorescence microscopy. The accumulation of various forms of PA (with acyl chains of 16:0-6:0, 16:0-12:0, 18:1-12:0) were compared to PC and the headgroup labeled phosphatidylethanolamine (PE), a lipid that has been shown to accumulate at regions of curvature. PA and PE accumulated more at tubules and led to the formation of more tubules than PC. Using large unilamellar liposomes in a dye-quenching assay, the location of the headgroup labeled PE was determined to be mostly on the outer, positively curved leaflet, whereas the tail labeled PA was located more on the inner, negatively curved leaflet. This study demonstrates that PA localizes to regions of negative curvature in liposomes and supports the formation of curved, tubulated membranes. This is one way that PA could be involved with curvature formation during a variety of cell processes. Full article
(This article belongs to the Special Issue Recent Developments in Biophysical Studies of Cell Membranes)
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Review

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61 pages, 21514 KiB  
Review
Leaflet Tensions Control the Spatio-Temporal Remodeling of Lipid Bilayers and Nanovesicles
by Reinhard Lipowsky, Rikhia Ghosh, Vahid Satarifard, Aparna Sreekumari, Miftakh Zamaletdinov, Bartosz Różycki, Markus Miettinen and Andrea Grafmüller
Biomolecules 2023, 13(6), 926; https://doi.org/10.3390/biom13060926 - 31 May 2023
Cited by 6 | Viewed by 1978
Abstract
Biological and biomimetic membranes are based on lipid bilayers, which consist of two monolayers or leaflets. To avoid bilayer edges, which form when the hydrophobic core of such a bilayer is exposed to the surrounding aqueous solution, a single bilayer closes up into [...] Read more.
Biological and biomimetic membranes are based on lipid bilayers, which consist of two monolayers or leaflets. To avoid bilayer edges, which form when the hydrophobic core of such a bilayer is exposed to the surrounding aqueous solution, a single bilayer closes up into a unilamellar vesicle, thereby separating an interior from an exterior aqueous compartment. Synthetic nanovesicles with a size below 100 nanometers, traditionally called small unilamellar vesicles, have emerged as potent platforms for the delivery of drugs and vaccines. Cellular nanovesicles of a similar size are released from almost every type of living cell. The nanovesicle morphology has been studied by electron microscopy methods but these methods are limited to a single snapshot of each vesicle. Here, we review recent results of molecular dynamics simulations, by which one can monitor and elucidate the spatio-temporal remodeling of individual bilayers and nanovesicles. We emphasize the new concept of leaflet tensions, which control the bilayers’ stability and instability, the transition rates of lipid flip-flops between the two leaflets, the shape transformations of nanovesicles, the engulfment and endocytosis of condensate droplets and rigid nanoparticles, as well as nanovesicle adhesion and fusion. To actually compute the leaflet tensions, one has to determine the bilayer’s midsurface, which represents the average position of the interface between the two leaflets. Two particularly useful methods to determine this midsurface are based on the density profile of the hydrophobic lipid chains and on the molecular volumes. Full article
(This article belongs to the Special Issue Recent Developments in Biophysical Studies of Cell Membranes)
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29 pages, 7575 KiB  
Review
Small-Angle Neutron Scattering for Studying Lipid Bilayer Membranes
by William T. Heller
Biomolecules 2022, 12(11), 1591; https://doi.org/10.3390/biom12111591 - 29 Oct 2022
Cited by 4 | Viewed by 3162
Abstract
Small-angle neutron scattering (SANS) is a powerful tool for studying biological membranes and model lipid bilayer membranes. The length scales probed by SANS, being from 1 nm to over 100 nm, are well-matched to the relevant length scales of the bilayer, particularly when [...] Read more.
Small-angle neutron scattering (SANS) is a powerful tool for studying biological membranes and model lipid bilayer membranes. The length scales probed by SANS, being from 1 nm to over 100 nm, are well-matched to the relevant length scales of the bilayer, particularly when it is in the form of a vesicle. However, it is the ability of SANS to differentiate between isotopes of hydrogen as well as the availability of deuterium labeled lipids that truly enable SANS to reveal details of membranes that are not accessible with the use of other techniques, such as small-angle X-ray scattering. In this work, an overview of the use of SANS for studying unilamellar lipid bilayer vesicles is presented. The technique is briefly presented, and the power of selective deuteration and contrast variation methods is discussed. Approaches to modeling SANS data from unilamellar lipid bilayer vesicles are presented. Finally, recent examples are discussed. While the emphasis is on studies of unilamellar vesicles, examples of the use of SANS to study intact cells are also presented. Full article
(This article belongs to the Special Issue Recent Developments in Biophysical Studies of Cell Membranes)
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Other

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13 pages, 329 KiB  
Perspective
Energy Dissipation in the Human Red Cell Membrane
by Thomas M. Fischer
Biomolecules 2023, 13(1), 130; https://doi.org/10.3390/biom13010130 - 09 Jan 2023
Viewed by 963
Abstract
The membrane of the human red cell consists of a lipid bilayer and a so-called membrane skeleton attached on the cytoplasmic side of the bilayer. Upon the deformation of red cells, energy is dissipated in their cytoplasm and their membrane. As to the [...] Read more.
The membrane of the human red cell consists of a lipid bilayer and a so-called membrane skeleton attached on the cytoplasmic side of the bilayer. Upon the deformation of red cells, energy is dissipated in their cytoplasm and their membrane. As to the membrane, three contributions can be distinguished: (i) A two-dimensional shear deformation with the membrane viscosity as the frictional parameter; (ii) A motion of the membrane skeleton relative to the bilayer; (iii) A relative motion of the two monolayers of the bilayer. The frictional parameter in contributions (ii) and (iii) is a frictional coefficient specific for the respective contribution. This perspective describes the history up to recent advances in the knowledge of these contributions. It reviews the mechanisms of energy dissipation on a molecular scale and suggests new ones, particularly for the first contribution. It proposes a parametric fitting expected to shed light on the discrepant values found for the membrane viscosity by different experimental approaches. It proposes strategies that could allow the determination of the frictional coefficients pertaining to the second and the third contribution. It highlights the consequences characteristic times have on the state of the red cell membrane in circulation as well as on the adaptation of computer models to the red cell history in an in vitro experiment. Full article
(This article belongs to the Special Issue Recent Developments in Biophysical Studies of Cell Membranes)
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