Mixing Temperatures of Bilayers Not Simply Related to Thickness Differences between L o and L d Phases

Bleecker, Joan V.; Cox, Phillip A.; Keller, Sarah L.

doi:10.1016/j.bpj.2016.03.042

Cited by 20 publications

(28 citation statements)

References 15 publications

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“…5). Commonly, the thermal stability of lateral domains is used as a measure of how prone a lipid mixture is to form domains (41,(48)(49)(50)(51). This parameter is mostly dependent on the lipid composition of the domains, and the higher the fraction of sterol and saturated PL is, the higher the melting temperature becomes.…”

Section: Lateral Segregationmentioning

confidence: 99%

The Affinity of Sterols for Different Phospholipid Classes and Its Impact on Lateral Segregation

Nyholm

Jaikishan

Engberg

et al. 2019

Biophysical Journal

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Cholesterol is an essential molecule in the membranes of mammalian cells. It is known to be distributed heterogeneously within the cells, between the bilayer leaflets, as well as between lateral domains within the bilayer. However, we do not know exactly how cholesterol is distributed and what forces drive this sorting process because it extremely difficult to study using currently available methods. To further elucidate this distribution, we measured how cholesterol partitions between different phospholipid (PL) environments using different methods based on cholesterol, TopFluor-cholesterol, and cholesta-5,7,9(11)-triene-3-b-ol. Based on the obtained relative partition coefficients, we made predictions regarding how cholesterol would be distributed between lateral domains and between the inner and outer leaflets of the plasma membrane. In addition, using a trans-parinaric acid fluorescence-based method, we tested how cholesterol could influence lateral segregation through its interaction with unsaturated PLs with different headgroups. The results showed that the lower the affinity of cholesterol was for the different unsaturated PLs, the more cholesterol stimulated lateral segregation in a ternary bilayer of unsaturated PL/ N-palmitoyl-D-erythro-sphingomyelin and cholesterol. Overall, the results indicate that both the distribution of cholesterol between different lipid environments and the impact of cholesterol on lateral segregation can be predicted relatively accurately from determined relative partition coefficients.

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Section: Lateral Segregationmentioning

confidence: 99%

The Affinity of Sterols for Different Phospholipid Classes and Its Impact on Lateral Segregation

Nyholm

Jaikishan

Engberg

et al. 2019

Biophysical Journal

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“…Saturated lipids and cholesterol constitute a rigid liquid ordered phase (l o ) in which acyl chains remain relatively straight. (84)(85)(86)(87) Unsaturated lipids form a more flexible liquid disordered phase (l do ) in which the chains remain fully melted. l o domains are often visualized as signaling "platforms", restricting membrane proteins into high density "rafts" that diffuse within a fluid membrane (88,89) .…”

Section: Introductionmentioning

confidence: 99%

Boundary lipids of the nicotinic acetylcholine receptor: Spontaneous partitioning via coarse-grained molecular dynamics simulation

Sharp¹,

Salari²,

Brannigan³

2019

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Reconstituted nicotinic acetylcholine receptors (nAChRs) exhibit significant gain-of-function upon addition of cholesterol to reconstitution mixtures, and cholesterol affects organization of nAChRs within domain-forming membranes, but whether nAChR partitions to cholesterol-rich liquid-ordered ("raft" or l o ) domains or cholesterol-poor liquiddisordered (l do ) domains is unknown. We use coarse-grained molecular dynamics simulations to observe spontaneous interactions of cholesterol, saturated lipids, and polyunsaturated (PUFA) lipids with nAChRs. In binary Dipalmitoylphosphatidylcholine:Cholesterol (DPPC:CHOL) mixtures, both CHOL and DPPC acyl chains were observed spontaneously entering deep "non-annular" cavities in the nAChR TMD, particularly at the subunit interface and the β subunit center, facilitated by the low amino acid density in the cryo-EM structure of nAChR in a native membrane. Cholesterol was highly enriched in the annulus around the TMD, but this effect extended over (at most) 5-10Å. In domain-forming ternary mixtures containing PUFAs, the presence of a single receptor did not significantly affect the likelihood of domain formation. nAChR partitioned to any cholesterol-poor l do domain that was present, regardless of whether the l do or l o domain lipids had PC or PE headgroups. Enrichment of PUFAs among boundary lipids was positively correlated with their propensity for demixing from cholesterol-rich phases. Long n − 3 chains (tested here with Docosahexaenoic Acid, DHA) were highly enriched in annular and non-annular embedded sites, partially displacing cholesterol and completely displacing DPPC, and occupying sites even deeper within the bundle. Shorter n − 6 chains were far less effective at displacing cholesterol from non-annular sites.

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“…While numerous phase diagrams are available that show coexisting immiscible liquid ordered-liquid disordered systems for both monolayers and bilayers (21-38), there are surprisingly few phase diagrams showing coexistence of two liquid condensed (LC), or semi-crystalline ordered phases, or transitions between ordered phases with temperature or surface pressure (39-42). This is likely due to the absence of fluorescent probes that selectively label liquid condensed or solid phases, which makes identifying the composition or even the existence of the two phases difficult.…”

Section: Introductionmentioning

confidence: 99%

Interfacial rheology of coexisting solid and fluid monolayers

et al. 2017

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Biologically relevant monolayer and bilayer films often consist of micron-scale high viscosity domains in a continuous low viscosity matrix. Here we show that this morphology can cause the overall monolayer fluidity to vary by orders of magnitude over a limited range of monolayer composition. Modeling the system as a two-dimensional suspension in analogy to classic three-dimensional suspensions of hard spheres in a liquid solvent explains the rheological data with no adjustable parameters. In monolayers with ordered, highly viscous domains dispersed in a continuous low viscosity matrix, the surface viscosity increases as a power law with the area fraction of viscous domains. Changing the phase of the continuous matrix from a disordered fluid phase to a more ordered, condensed phase dramatically changes the overall monolayer viscosity. Small changes in the domain density and/or continuous matrix composition can alter themonolayerviscosity by orders of magnitude.

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Mixing Temperatures of Bilayers Not Simply Related to Thickness Differences between L o and L d Phases

Cited by 20 publications

References 15 publications

The Affinity of Sterols for Different Phospholipid Classes and Its Impact on Lateral Segregation

The Affinity of Sterols for Different Phospholipid Classes and Its Impact on Lateral Segregation

Boundary lipids of the nicotinic acetylcholine receptor: Spontaneous partitioning via coarse-grained molecular dynamics simulation

Interfacial rheology of coexisting solid and fluid monolayers

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