Special Issue "Plasma Membrane Lipid Domains As a Favorable Environment for Protein:Lipid Interactions?"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (4 October 2019).

Special Issue Editor

Dr. Donatienne Tyteca
E-Mail Website
Guest Editor
CELL Unit, de Duve Institute & Université catholique de Louvain, 1200 Brussels, Belgium
Interests: lipid domains; vital confocal imaging; lipid probes; red blood cell deformation; cancer cell migration; cell vesiculation; cytoskeleton; membrane curvature ; membrane lipid order; membrane asymmetry

Special Issue Information

Dear colleagues,

The surface of living cells provides an interface that not only separates the outer and inner environments but also contributes to several functions, including the regulation of solute influx and efflux, signal transduction, lipid metabolism and trafficking. To fulfill these roles, the cell surface must be tough and plastic at the same time. This could explain why cell membranes exhibit such a large variety of lipid species and why some lipids cluster into membrane domains. These domains have been reported during the past decades in a variety of living cells from prokaryotes to yeast and mammalian cells, thanks to powerful and innovative approaches. The domains vary in size, stability, lipid composition, biophysical properties (e.g. lipid order, curvature, thickness) and dependence to extrinsic factors (e.g. cytoskeleton, charged headgroup:cation electrostatic interactions, membrane recycling and enzymatic modifications).

Due to diversity in the lipid composition and properties, domains could serve as recruitment or exclusion platforms for specific membrane proteins, thereby participating in the spatiotemporal regulation of dynamic cellular events. One major challenge of this fascinating field is to determine how membrane biophysical properties and extrinsic factors could contribute to protein confinement in domains. Another challenge is to evaluate whether proteins localize in the resting state into domains that are needed for their primary activation or whether proteins are able to recruit specific lipids in their surrounding environment, thereby forming domains with appropriate biophysical properties.

In this Special Issue, thanks to the integration of theoretical work and data obtained on model membranes and living cells (from prokaryotes to yeast and mammalian cells), we expect to shed new light on various aspects of protein activity through their confinement in, or exclusion from, plasma membrane domains.

Dr. Donatienne Tyteca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lipid domains
  • simulation studies
  • model membranes
  • living cells
  • protein:lipid interaction
  • protein confinement
  • cytoskeleton
  • membrane curvature
  • membrane lipid order
  • membrane asymmetry

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

Article
Structural Lesions of Proteins Connected to Lipid Membrane Damages Caused by Radical Stress: Assessment by Biomimetic Systems and Raman Spectroscopy
Biomolecules 2019, 9(12), 794; https://doi.org/10.3390/biom9120794 - 27 Nov 2019
Cited by 6 | Viewed by 1156
Abstract
Model systems constituted by proteins and unsaturated lipid vesicles were used to gain more insight into the effects of the propagation of an initial radical damage on protein to the lipid compartment. The latter is based on liposome technology and allows measuring the [...] Read more.
Model systems constituted by proteins and unsaturated lipid vesicles were used to gain more insight into the effects of the propagation of an initial radical damage on protein to the lipid compartment. The latter is based on liposome technology and allows measuring the trans unsaturated fatty acid content as a result of free radical stress on proteins. Two kinds of sulfur-containing proteins were chosen to connect their chemical reactivity with membrane lipid transformation, serum albumins and metallothioneins. Biomimetic systems based on radiation chemistry were used to mimic the protein exposure to different kinds of free radical stress and Raman spectroscopy to shed light on protein structural changes caused by the free radical attack. Among the amino acid residues, Cys is one of the most sensitive residues towards the attack of free radicals, thus suggesting that metal-Cys clusters are good interceptors of reactive species in metallothioneins, together with disulfides moieties in serum albumins. Met is another important site of the attack, in particular under reductive conditions. Tyr and Phe are sensitive to radical stress too, leading to electron transfer reactions or radical-induced modifications of their structures. Finally, modifications in protein folding take place depending on reactive species attacking the protein. Full article
Show Figures

Graphical abstract

Article
The Effect of Transmembrane Protein Shape on Surrounding Lipid Domain Formation by Wetting
Biomolecules 2019, 9(11), 729; https://doi.org/10.3390/biom9110729 - 12 Nov 2019
Cited by 3 | Viewed by 1050
Abstract
Signal transduction through cellular membranes requires the highly specific and coordinated work of specialized proteins. Proper functioning of these proteins is provided by an interplay between them and the lipid environment. Liquid-ordered lipid domains are believed to be important players here, however, it [...] Read more.
Signal transduction through cellular membranes requires the highly specific and coordinated work of specialized proteins. Proper functioning of these proteins is provided by an interplay between them and the lipid environment. Liquid-ordered lipid domains are believed to be important players here, however, it is still unclear whether conditions for a phase separation required for lipid domain formation exist in cellular membranes. Moreover, membrane leaflets are compositionally asymmetric, that could be an obstacle for the formation of symmetric domains spanning the lipid bilayer. We theoretically show that the presence of protein in the membrane leads to the formation of a stable liquid-ordered lipid phase around it by the mechanism of protein wetting by lipids, even in the absence of conditions necessary for the global phase separation in the membrane. Moreover, we show that protein shape plays a crucial role in this process, and protein conformational rearrangement can lead to changes in the size and characteristics of surrounding lipid domains. Full article
Show Figures

Figure 1

Article
Interaction of a Polyarginine Peptide with Membranes of Different Mechanical Properties
Biomolecules 2019, 9(10), 625; https://doi.org/10.3390/biom9100625 - 18 Oct 2019
Cited by 10 | Viewed by 1587
Abstract
The membrane translocation efficiency of cell penetrating peptides (CPPs) has been largely studied, and poly-arginines have been highlighted as particularly active CPPs, especially upon negatively charged membranes. Here we inquire about the influence of membrane mechanical properties in poly-arginine adsorption, penetration and translocation, [...] Read more.
The membrane translocation efficiency of cell penetrating peptides (CPPs) has been largely studied, and poly-arginines have been highlighted as particularly active CPPs, especially upon negatively charged membranes. Here we inquire about the influence of membrane mechanical properties in poly-arginine adsorption, penetration and translocation, as well as the subsequent effect on the host membrane. For this, we selected anionic membranes exhibiting different rigidity and fluidity, and exposed them to the nona-arginine KR9C. Three different membrane compositions were investigated, all of them having 50% of the anionic lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DOPG), thus, ensuring a high affinity of the peptide for membrane surfaces. The remaining 50% was a saturated PC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC), an unsaturated PC (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) or a mixture of DOPC with cholesterol. Peptide-membrane interactions were studied using four complementary models for membranes: Langmuir monolayers, Large Unilamellar Vesicles, Black Lipid Membranes and Giant Unilamellar Vesicles. The patterns of interaction of KR9C varied within the different membrane compositions. The peptide strongly adsorbed on membranes with cholesterol, but did not incorporate or translocate them. KR9C stabilized phase segregation in DPPC/DOPG films and promoted vesicle rupture. DOPC/DOPG appeared like the better host for peptide translocation: KR9C adsorbed, inserted and translocated these membranes without breaking them, despite softening was observed. Full article
Show Figures

Graphical abstract

Article
Role of Transmembrane Proteins for Phase Separation and Domain Registration in Asymmetric Lipid Bilayers
Biomolecules 2019, 9(8), 303; https://doi.org/10.3390/biom9080303 - 25 Jul 2019
Cited by 3 | Viewed by 1640
Abstract
It is well known that the formation and spatial correlation of lipid domains in the two apposed leaflets of a bilayer are influenced by weak lipid–lipid interactions across the bilayer’s midplane. Transmembrane proteins span through both leaflets and thus offer an alternative domain [...] Read more.
It is well known that the formation and spatial correlation of lipid domains in the two apposed leaflets of a bilayer are influenced by weak lipid–lipid interactions across the bilayer’s midplane. Transmembrane proteins span through both leaflets and thus offer an alternative domain coupling mechanism. Using a mean-field approximation of a simple bilayer-type lattice model, with two two-dimensional lattices stacked one on top of the other, we explore the role of this “structural” inter-leaflet coupling for the ability of a lipid membrane to phase separate and form spatially correlated domains. We present calculated phase diagrams for various effective lipid–lipid and lipid–protein interaction strengths in membranes that contain a binary lipid mixture in each leaflet plus a small amount of added transmembrane proteins. The influence of the transmembrane nature of the proteins is assessed by a comparison with “peripheral” proteins, which result from the separation of one single integral protein into two independent units that are no longer structurally connected across the bilayer. We demonstrate that the ability of membrane-spanning proteins to facilitate domain formation requires sufficiently strong lipid–protein interactions. Weak lipid–protein interactions generally tend to inhibit phase separation in a similar manner for transmembrane as for peripheral proteins. Full article
Show Figures

Figure 1

Article
Membrane Localization of HspA1A, a Stress Inducible 70-kDa Heat-Shock Protein, Depends on Its Interaction with Intracellular Phosphatidylserine
Biomolecules 2019, 9(4), 152; https://doi.org/10.3390/biom9040152 - 17 Apr 2019
Cited by 8 | Viewed by 2441
Abstract
HspA1A is a cytosolic molecular chaperone essential for cellular homeostasis. HspA1A also localizes at the plasma membrane (PM) of tumor and stressed cells. However, it is currently unknown how this cytosolic protein translocates to the PM. Taking into account that HspA1A interacts with [...] Read more.
HspA1A is a cytosolic molecular chaperone essential for cellular homeostasis. HspA1A also localizes at the plasma membrane (PM) of tumor and stressed cells. However, it is currently unknown how this cytosolic protein translocates to the PM. Taking into account that HspA1A interacts with lipids, including phosphatidylserine (PS), and that lipids recruit proteins to the PM, we hypothesized that the interaction of HspA1A with PS allows the chaperone to localize at the PM. To test this hypothesis, we subjected cells to mild heat-shock and the PM-localized HspA1A was quantified using confocal microscopy and cell surface biotinylation. These experiments revealed that HspA1A’s membrane localization increased during recovery from non-apoptotic heat-shock. Next, we selectively reduced PS targets by overexpressing the C2 domain of lactadherin (Lact-C2), a known PS-biosensor, and determined that HspA1A’s membrane localization was greatly reduced. In contrast, the reduction of PI(4,5)P2 availability by overexpression of the PLCδ-PH biosensor had minimal effects on HspA1A’s PM-localization. Implementation of a fluorescent PS analog, TopFluor-PS, established that PS co-localizes with HspA1A. Collectively, these results reveal that HspA1A’s PM localization and anchorage depend on its selective interaction with intracellular PS. This discovery institutes PS as a new and dynamic partner in the cellular stress response. Full article
Show Figures

Figure 1

Review

Jump to: Research, Other

Review
Regulation of Membrane Calcium Transport Proteins by the Surrounding Lipid Environment
Biomolecules 2019, 9(10), 513; https://doi.org/10.3390/biom9100513 - 20 Sep 2019
Cited by 12 | Viewed by 2073
Abstract
Calcium ions (Ca2+) are major messengers in cell signaling, impacting nearly every aspect of cellular life. Those signals are generated within a wide spatial and temporal range through a large variety of Ca2+ channels, pumps, and exchangers. More and more [...] Read more.
Calcium ions (Ca2+) are major messengers in cell signaling, impacting nearly every aspect of cellular life. Those signals are generated within a wide spatial and temporal range through a large variety of Ca2+ channels, pumps, and exchangers. More and more evidences suggest that Ca2+ exchanges are regulated by their surrounding lipid environment. In this review, we point out the technical challenges that are currently being overcome and those that still need to be defeated to analyze the Ca2+ transport protein–lipid interactions. We then provide evidences for the modulation of Ca2+ transport proteins by lipids, including cholesterol, acidic phospholipids, sphingolipids, and their metabolites. We also integrate documented mechanisms involved in the regulation of Ca2+ transport proteins by the lipid environment. Those include: (i) Direct interaction inside the protein with non-annular lipids; (ii) close interaction with the first shell of annular lipids; (iii) regulation of membrane biophysical properties (e.g., membrane lipid packing, thickness, and curvature) directly around the protein through annular lipids; and (iv) gathering and downstream signaling of several proteins inside lipid domains. We finally discuss recent reports supporting the related alteration of Ca2+ and lipids in different pathophysiological events and the possibility to target lipids in Ca2+-related diseases. Full article
Show Figures

Figure 1

Review
Role of MCC/Eisosome in Fungal Lipid Homeostasis
Biomolecules 2019, 9(8), 305; https://doi.org/10.3390/biom9080305 - 25 Jul 2019
Cited by 17 | Viewed by 1832
Abstract
One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich plasma membrane domain. It is stabilized on its cytosolic face by the eisosome, a hemitubular protein complex composed of Bin/Amphiphysin/Rvs (BAR) [...] Read more.
One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich plasma membrane domain. It is stabilized on its cytosolic face by the eisosome, a hemitubular protein complex composed of Bin/Amphiphysin/Rvs (BAR) domain-containing Pil1 and Lsp1. These two proteins bind directly to phosphatidylinositol 4,5-bisphosphate and promote the typical furrow-like shape of the microdomain, with highly curved edges and bottom. While some proteins display stable localization in the MCC/eisosome, others enter or leave it under particular conditions, such as misbalance in membrane lipid composition, changes in membrane tension, or availability of specific nutrients. These findings reveal that the MCC/eisosome, a plasma membrane microdomain with distinct morphology and lipid composition, acts as a multifaceted regulator of various cellular processes including metabolic pathways, cellular morphogenesis, signalling cascades, and mRNA decay. In this minireview, we focus on the MCC/eisosome’s proposed role in the regulation of lipid metabolism. While the molecular mechanisms of the MCC/eisosome function are not completely understood, the idea of intracellular processes being regulated at the plasma membrane, the foremost barrier exposed to environmental challenges, is truly exciting. Full article
Show Figures

Figure 1

Other

Jump to: Research, Review

Opinion
Coupled Response of Membrane Hydration with Oscillating Metabolism in Live Cells: An Alternative Way to Modulate Structural Aspects of Biological Membranes?
Biomolecules 2019, 9(11), 687; https://doi.org/10.3390/biom9110687 - 02 Nov 2019
Cited by 6 | Viewed by 1021
Abstract
We propose that active metabolic processes may regulate structural changes in biological membranes via the physical state of cell water. This proposition is based on recent results obtained from our group in yeast cells displaying glycolytic oscillations, where we demonstrated that there is [...] Read more.
We propose that active metabolic processes may regulate structural changes in biological membranes via the physical state of cell water. This proposition is based on recent results obtained from our group in yeast cells displaying glycolytic oscillations, where we demonstrated that there is a tight coupling between the oscillatory behavior of glycolytic metabolites (ATP, NADH) and the extent of the dipolar relaxation of intracellular water, which oscillates synchronously. The mechanism we suggest involves the active participation of a polarized intracellular water network whose degree of polarization is dynamically modulated by temporal ATP fluctuations caused by metabolism with intervention of a functional cytoskeleton, as conceived in the long overlooked association-induction hypothesis (AIH) of Gilbert Ling. Our results show that the polarized state of intracellular water can be propagated from the cytosol to regions containing membranes. Since changes in the extent of the polarization of water impinge on its chemical activity, we hypothesize that metabolism dynamically controls the local structure of cellular membranes via lyotropic effects. This hypothesis offers an alternative way to interpret membrane related phenomena (e.g., changes in local curvature pertinent to endo/exocytosis or dynamical changes in membranous organelle structure, among others) by integrating relevant but mostly overlooked physicochemical characteristics of the cellular milieu. Full article
Show Figures

Figure 1

Back to TopTop