scholarly journals The Effect of Transmembrane Protein Shape on Surrounding Lipid Domain Formation by Wetting

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 729 ◽  
Author(s):  
Molotkovsky ◽  
Galimzyanov ◽  
Batishchev ◽  
Akimov
Keyword(s):  
Phase Separation ◽  
Transmembrane Protein ◽  
Lipid Phase ◽  
Lipid Domains ◽  
Domain Formation ◽  
Cellular Membranes ◽  
Lipid Domain ◽  
Liquid Ordered ◽  
Lipid Environment ◽  
Protein Shape

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.

scholarly journals Regimes of Complex Lipid Bilayer Phases Induced by Cholesterol Concentration in MD Simulation

2018 ◽  
Author(s):  
George A. Pantelopulos ◽  
John E. Straub
Keyword(s):  
Phase Separation ◽  
Cholesterol Concentration ◽  
Lipid Domains ◽  
Lipid Mixture ◽  
Knowledge Models ◽  
Lipid Mixtures ◽  
Mixture Phase ◽  
Liquid Ordered ◽  
Dynamics Simulations ◽  
And Function

AbstractCholesterol is essential to the formation of phase separated lipid domains in membranes. Lipid domains can exist in different thermodynamic phases depending on the molecular composition, and play significant roles in determining structure and function of membrane proteins. We investigate the role of cholesterol in the structure and dynamics of ternary lipid mixtures displaying phase separation using Molecular Dynamics simulations, employing a physiologically-relevant span of cholesterol concentration. We find that cholesterol can induce formation of three regimes of phase behavior, I) miscible liquid disordered bulk, II) phase separated, domain registered coexistence of liquid disordered and liquid ordered and domains, and III) phase separated, domain-anti-registered coexistence of liquid-disordered and newly-identified nanoscopic gel domains composed of cholesterol threads we name “cholesterolic gel” domains. These findings are validated and discussed in the context of current experimental knowledge, models of cholesterol spatial distributions, and models of ternary lipid mixture phase separation.

scholarly journals Cholesterol-dependent phase separation in cell-derived giant plasma-membrane vesicles

2009 ◽  
Vol 424 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Ilya Levental ◽  
Fitzroy J. Byfield ◽  
Pramit Chowdhury ◽  
Feng Gai ◽  
Tobias Baumgart ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Phase Separation ◽  
Membrane Vesicles ◽  
Correlation Spectroscopy ◽  
Model Systems ◽  
Live Cells ◽  
Lipid Phase ◽  
Plasma Membrane Vesicles ◽  
Liquid Ordered ◽  
Lipid Phase Separation

Cell-derived GPMVs (giant plasma-membrane vesicles) enable investigation of lipid phase separation in a system with appropriate biological complexity under physiological conditions, and in the present study were used to investigate the cholesterol-dependence of domain formation and stability. The cholesterol level is directly related to the abundance of the liquid-ordered phase fraction, which is the majority phase in vesicles from untreated cells. Miscibility transition temperature depends on cholesterol and correlates strongly with the presence of detergent-insoluble membrane in cell lysates. Fluorescence correlation spectroscopy reveals two distinct diffusing populations in phase-separated cell membrane-derived vesicles whose diffusivities correspond well to diffusivities in both model systems and live cells. The results of the present study extend previous observations in purified lipid systems to the complex environment of the plasma membrane and provide insight into the effect of cholesterol on lipid phase separation and abundance.

scholarly journals Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells

2013 ◽  
Vol 202 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Alexandre Toulmay ◽  
William A. Prinz
Keyword(s):  
Vesicular Trafficking ◽  
Live Cells ◽  
Membrane Rafts ◽  
Lipid Domains ◽  
Domain Formation ◽  
Ph Responsive ◽  
Vacuole Membrane ◽  
Liquid Ordered ◽  
Micrometer Scale ◽  
In Cells

It has been proposed that membrane rafts, which are sterol- and sphingolipid-enriched liquid-ordered (Lo) domains, segregate proteins in membranes and play critical roles in numerous processes in cells. However, rafts remain controversial because they are difficult to observe in cells without invasive methods and seem to be very small (nanoscale) and short lived, leading many to question whether they exist or are physiologically relevant. In this paper, we show that micrometer-scale, stable lipid domains formed in the yeast vacuole membrane in response to nutrient deprivation, changes in the pH of the growth medium, and other stresses. All vacuolar membrane proteins tested segregated to one of two domains. These domains formed quasi-symmetrical patterns strikingly similar to those found in liposomes containing coexisting Lo and liquid-disordered regions. Indeed, we found that one of these domains is probably sterol enriched and Lo. Domain formation was shown to be regulated by the pH-responsive Rim101 signaling pathway and may also require vesicular trafficking to vacuoles.

scholarly journals Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids

2020 ◽  
Vol 61 (5) ◽  
pp. 758-766 ◽  
Author(s):  
Guangtao Li ◽  
Qing Wang ◽  
Shinako Kakuda ◽  
Erwin London
Keyword(s):  
Plasma Membrane ◽  
Phase Separation ◽  
Light Microscopy ◽  
Large Scale ◽  
Membrane Vesicles ◽  
Lipid Domains ◽  
Domain Formation ◽  
Plasma Membrane Vesicles ◽  
Intact Cells ◽  
Wide Range

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.

Lipids and lipid domains of the yeast vacuole

2018 ◽  
Vol 46 (5) ◽  
pp. 1047-1054 ◽  
Author(s):  
Takuma Tsuji ◽  
Toyoshi Fujimoto
Keyword(s):  
Stationary Phase ◽  
Living Cell ◽  
Vacuolar Membrane ◽  
Lipid Domains ◽  
Sterol Content ◽  
Domain Formation ◽  
Membrane Raft ◽  
The Past ◽  
Yeast Vacuole ◽  
Liquid Ordered

The membrane raft has been a focus of intensive research for the past two decades. Liquid-ordered domains form in artificial liposomes containing sterol and saturated lipids, but their presence in living cell membranes has been controversial. The yeast vacuole is exceptional in that micron-sized raft-like domains form in the stationary phase and under several other conditions. The sterol content of the vacuole in the log phase is much lower than that of liposomes showing liquid-ordered domains, suggesting that sterols may need to be supplied to the vacuole for the raft-like domain formation. We will discuss how lipids and lipid domains are organized in the vacuolar membrane and examine whether evidence is strong enough to conclude that the observed micron-sized domains are rafts.

scholarly journals Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Katie D. Hickey ◽  
Mary M. Buhr
Keyword(s):  
Lipid Bilayer ◽  
Lipid Composition ◽  
Protein Function ◽  
Transmembrane Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Outer Leaflet ◽  
Lipid Environment ◽  
Protein Incorporation ◽  
And Function

Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+K+-ATPase or -amylase). Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET) confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+K+-ATPase within the membranes.

scholarly journals Elucidating the structural features of ABCA1 in its heterogeneous membrane environment.

2021 ◽  
Author(s):  
Sunidhi S ◽  
Sukriti Sacher ◽  
Parth Garg ◽  
Arjun Ray
Keyword(s):  
Conformational Changes ◽  
Transmembrane Protein ◽  
Direct Interaction ◽  
Structural Features ◽  
Lipid Binding ◽  
Lipid Monolayer ◽  
Alternative Theory ◽  
Lipid Dynamics ◽  
Lipid Environment ◽  
Dynamics Simulations

ABCA1 plays an integral part in Reverse Cholesterol Transport (RCT) and is critical for maintaining lipid homeostasis. One theory of lipid efflux by the transporter (alternating access) proposes that ABCA1 harbors two different conformations that provide alternate access for lipid binding and release, leading to sequestration via a direct interaction between ABCA1 and its partner, ApoA1. The alternative theory (lateral access) proposes that ABCA1 obtains lipids laterally from the membrane to form a temporary extracellular reservoir containing an isolated pressurized lipid monolayer caused by the net accumulation of lipids in the exofacial leaflet. Recently, a full-length Cryo-EM structure of this 2,261-residue transmembrane protein showed its discreetly folded domains and conformations, as well as detected the presence of a tunnel enclosed within ECDs. While the tunnel was wide enough at the proximal end for accommodating passage of lipids, the distal end displayed substantial narrowing, making it inaccessible for ApoA1. Therefore, this structure was hypothesized to substantiate the lateral access theory, whereby ApoA1 obtained lipids from the proximal end. Utilizing long time-scale multiple replica atomistic molecular dynamics simulations (MDS), we simulated the structure in a heterogeneous lipid environment and found that along with several large conformational changes, the protein widens enough at the distal end of its ECD tunnel to now enable lipid accommodation. In this study we have characterized ABCA1 and the lipid dynamics along with the protein-lipid interactions in the heterogeneous environment, providing novel insights into understanding ABCA1 conformation at an atomistic level.

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