Limits...
Modulation of a small two-domain lipid vesicle by linactants.

Li Z, Gorfe AA - J Phys Chem B (2014)

Bottom Line: We found that addition of a small amount of linactants (∼1%) to a two-domain vesicle leads to substantial reduction in the line tension and neck curvature at the domain boundary.Using cross-linking as a surrogate for clustering, we further show that linactant clusters substantially enhance the boundary preference and therefore the reduction in neck curvature.These results have important implications for the potential existence and physical explanations of nanosized domains in biological membranes.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston , 6431 Fannin Street, Houston, Texas 77030, United States.

ABSTRACT
Linactants, molecules that preferentially localize at the boundary of lipid membrane domains, are attracting considerable attention in recent years due to the recognition that they might regulate lipid-phase separation and thereby modulate membrane morphology. Recent studies have also shown that clustering of some line active agents enhances their ability to modulate membrane curvature. However, the molecular origin of this phenomenon, and the degree to which it impacts biological membranes, remains poorly understood. In this work, we have investigated how linactants induce shape change in multidomain small unilamallar vesicles (SUVs) using extensive dissipative particle dynamics simulations. The linactant was modeled as a two-tailed hybrid lipid with the two tails differing in preference for different lipid domains. We found that addition of a small amount of linactants (∼1%) to a two-domain vesicle leads to substantial reduction in the line tension and neck curvature at the domain boundary. Using cross-linking as a surrogate for clustering, we further show that linactant clusters substantially enhance the boundary preference and therefore the reduction in neck curvature. Moreover, on the basis of analyses of the corresponding changes in the membrane energetics, we highlight how linactants might stabilize nanoscale domains. These results have important implications for the potential existence and physical explanations of nanosized domains in biological membranes.

Show MeSH

Related in: MedlinePlus

Lateraldistribution and effect of linactants on a two-domain bilayer.(a) Final snapshot of a reference two-domain bilayer without hybridlipids. (b) Final snapshot of a two-domain bilayer containing 100monomeric linactants. In each case, the blue line represents the actualsimulation box. Red dots represent lipid A and blue dots lipid B,while green spheres represent the hybrid lipid. (c) Line tension ofa two-domain bilayer as a function of the number of linactants perunit length (line number density) of the domain boundary.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4120979&req=5

fig4: Lateraldistribution and effect of linactants on a two-domain bilayer.(a) Final snapshot of a reference two-domain bilayer without hybridlipids. (b) Final snapshot of a two-domain bilayer containing 100monomeric linactants. In each case, the blue line represents the actualsimulation box. Red dots represent lipid A and blue dots lipid B,while green spheres represent the hybrid lipid. (c) Line tension ofa two-domain bilayer as a function of the number of linactants perunit length (line number density) of the domain boundary.

Mentions: For bilayers containingtwo stripped domains, the domain boundarywas found to be a ∼5d0-wide interfacecharacterized by a sharp transition in lipid composition (Figure 4a). The boundary line tension σ was estimatedfrom the pressure tensors (eq 8)498where Lx and Lz are thesimulation box lengths along the x and z dimensions, respectively, and Pxx and Pyy are therespective pressure tensors perpendicular and parallel to the domainboundary along the x dimension. σ was estimatedto be 4.38 ± 0.08kbT/d0 for the linactant-free bilayer (Figure 4c), which is sufficientlylarge to induce lipid-phase separation and maintain a fluctuatingboundary. The addition of hybrid lipids did not affect the phase separationbehavior, but their accumulation at the boundary appears to increasethe extent of the boundary fluctuation (Figure 4b). To estimate the efficacy of the linactants to reduce line tension,we calculated σ and the line number density of linactants atthe domain boundary assuming uniform distribution (i.e., number oflinactants at the boundary per unit length). This was done for bilayerscontaining the same number of A- and B-type lipids but different totalnumber of linactants (0, 100, 200, 300). The plot in Figure 4c shows that σ is correlated linearly withthe number density, indicating that in all simulations the linactantconcentration was small and does not saturate the boundary region.The slope of a linear fit of this curve quantifies the reduction inline tension per linactant molecule, which is equal to −0.50kbT. Clearly, accumulation oflinactants at domain boundaries significantly reduces the line tension.


Modulation of a small two-domain lipid vesicle by linactants.

Li Z, Gorfe AA - J Phys Chem B (2014)

Lateraldistribution and effect of linactants on a two-domain bilayer.(a) Final snapshot of a reference two-domain bilayer without hybridlipids. (b) Final snapshot of a two-domain bilayer containing 100monomeric linactants. In each case, the blue line represents the actualsimulation box. Red dots represent lipid A and blue dots lipid B,while green spheres represent the hybrid lipid. (c) Line tension ofa two-domain bilayer as a function of the number of linactants perunit length (line number density) of the domain boundary.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120979&req=5

fig4: Lateraldistribution and effect of linactants on a two-domain bilayer.(a) Final snapshot of a reference two-domain bilayer without hybridlipids. (b) Final snapshot of a two-domain bilayer containing 100monomeric linactants. In each case, the blue line represents the actualsimulation box. Red dots represent lipid A and blue dots lipid B,while green spheres represent the hybrid lipid. (c) Line tension ofa two-domain bilayer as a function of the number of linactants perunit length (line number density) of the domain boundary.
Mentions: For bilayers containingtwo stripped domains, the domain boundarywas found to be a ∼5d0-wide interfacecharacterized by a sharp transition in lipid composition (Figure 4a). The boundary line tension σ was estimatedfrom the pressure tensors (eq 8)498where Lx and Lz are thesimulation box lengths along the x and z dimensions, respectively, and Pxx and Pyy are therespective pressure tensors perpendicular and parallel to the domainboundary along the x dimension. σ was estimatedto be 4.38 ± 0.08kbT/d0 for the linactant-free bilayer (Figure 4c), which is sufficientlylarge to induce lipid-phase separation and maintain a fluctuatingboundary. The addition of hybrid lipids did not affect the phase separationbehavior, but their accumulation at the boundary appears to increasethe extent of the boundary fluctuation (Figure 4b). To estimate the efficacy of the linactants to reduce line tension,we calculated σ and the line number density of linactants atthe domain boundary assuming uniform distribution (i.e., number oflinactants at the boundary per unit length). This was done for bilayerscontaining the same number of A- and B-type lipids but different totalnumber of linactants (0, 100, 200, 300). The plot in Figure 4c shows that σ is correlated linearly withthe number density, indicating that in all simulations the linactantconcentration was small and does not saturate the boundary region.The slope of a linear fit of this curve quantifies the reduction inline tension per linactant molecule, which is equal to −0.50kbT. Clearly, accumulation oflinactants at domain boundaries significantly reduces the line tension.

Bottom Line: We found that addition of a small amount of linactants (∼1%) to a two-domain vesicle leads to substantial reduction in the line tension and neck curvature at the domain boundary.Using cross-linking as a surrogate for clustering, we further show that linactant clusters substantially enhance the boundary preference and therefore the reduction in neck curvature.These results have important implications for the potential existence and physical explanations of nanosized domains in biological membranes.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston , 6431 Fannin Street, Houston, Texas 77030, United States.

ABSTRACT
Linactants, molecules that preferentially localize at the boundary of lipid membrane domains, are attracting considerable attention in recent years due to the recognition that they might regulate lipid-phase separation and thereby modulate membrane morphology. Recent studies have also shown that clustering of some line active agents enhances their ability to modulate membrane curvature. However, the molecular origin of this phenomenon, and the degree to which it impacts biological membranes, remains poorly understood. In this work, we have investigated how linactants induce shape change in multidomain small unilamallar vesicles (SUVs) using extensive dissipative particle dynamics simulations. The linactant was modeled as a two-tailed hybrid lipid with the two tails differing in preference for different lipid domains. We found that addition of a small amount of linactants (∼1%) to a two-domain vesicle leads to substantial reduction in the line tension and neck curvature at the domain boundary. Using cross-linking as a surrogate for clustering, we further show that linactant clusters substantially enhance the boundary preference and therefore the reduction in neck curvature. Moreover, on the basis of analyses of the corresponding changes in the membrane energetics, we highlight how linactants might stabilize nanoscale domains. These results have important implications for the potential existence and physical explanations of nanosized domains in biological membranes.

Show MeSH
Related in: MedlinePlus