Carla Rosetti - Academia.edu (original) (raw)

Papers by Carla Rosetti

Journal of Physical Chemistry B, Feb 10, 2017

Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was pr... more Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was proposed that hybrid lipids, with mixed saturated and unsaturated acyl chains, participate in the relaxation of γ through different mechanisms. In this work, we used molecular dynamics simulations of the coarse-grained MARTINI model to measure γ in liquid-ordered−liquid-disordered (Lo−Ld) membranes, with increasingly larger relative proportion of the hybrid polyunsaturated lipid PAPC (4:0−5:4PC) to DAPC (di5:4PC) (i.e., X H). We also calculated an elastic contribution to γ by the Lo−Ld thickness mismatch, tilt moduli, and bending moduli, as predicted by theory. We found that an increase in X H decreased the overall γ value and the elastic contribution to line tension. The effect on the elastic line tension is driven by a reduced hydrophobic mismatch. Changes in the elastic constants of the phases due to an increase in X H produced a slightly larger elastic γ term. In addition to this elastic energy, other major contributions to γ are found in these model membranes. Increasing X H decreases both elastic and nonelastic contributions to γ. Finally, PAPC also behaves as a linactant, relaxing γ through an interfacial effect, as predicted by theoretical results. This study gives insight into the actual contribution of distinct energy terms to γ in bilayers containing polyunsaturated hybrid lipids.

Journal of Physical Chemistry B, Mar 9, 2012

We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an uns... more We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an unsaturated lipid, and a fully saturated lipid, by means of molecular dynamics simulations of the MARTINI coarse grain model. We aimed at comparing lateral organization and local properties of bilayers containing phosphatidylcholine (PC) lipids, either with two unsaturated tails (symmetric), or one unsaturated and one saturated tail (asymmetric), as the low-melting component of the mixture. The number of unsaturations per chain was systematically varied in both classes of unsaturated lipids, to account for its consequences in segregation. In the asymmetric unsaturated PCs, the saturated tail was kept identical to the hydrophobic chains of the fully saturated lipid component. Membranes with a symmetric or an asymmetric unsaturated lipid, with the same kind of unsaturated chain, show different phase behavior. Symmetric polyunsaturated PCs set the separation in two phases. Instead, the asymmetric polyunsaturated lipids induced nonideal mixing of components in single-phase bilayers. A significative drop of temperature, within the accessible temperature range, enhances the segregation in mixtures with the more unsaturated asymmetric PC, but still within a single phase. This different phase behavior between membranes with symmetric and asymmetric unsaturated PCs is also observed for lipids with the same total number of unsaturations. On the other hand, the degree of unsaturation per se enhances the segregation, by increasing the composition fluctuations in single-phase membranes with asymmetric PC lipids, and raising the line tension in the two-phase bilayer mixtures with symmetric polyunsaturated PCs. Dynamic clusters of unsaturated asymmetric lipids can be identified. The clusters show no correlation between leaflets, as observed for the phase domains in mixtures with the symmetric polyunsaturated PCs. Interestingly, we found that asymmetric PC lipids have a preferential orientation such that their saturated tails increase their density toward the periphery of the clusters, facing regions enriched in the fully saturated lipids and cholesterol. The degree of unsaturation increases the cluster size and also enhances the anisotropy of the orientation. The surface density of cholesterol follows a gradient that favors its interaction with the saturated tails. Such gradients in composition lead to gradients in order parameters, such as the conformational order and the area of the tails, which increases away from the unsaturated lipid clusters. We compared, in addition, differences in hydrophobic length mismatch between acyl chains of the low-melting and high-melting components, in mixtures containing either symmetric or asymmetric unsaturated lipids.

Journal of Physical Chemistry B, Dec 28, 2010

The Journal of Physical Chemistry B, 2017

Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was pr... more Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was proposed that hybrid lipids, with mixed saturated and unsaturated acyl chains, participate in the relaxation of γ through different mechanisms. In this work, we used molecular dynamics simulations of the coarse-grained MARTINI model to measure γ in liquid-ordered−liquid-disordered (Lo−Ld) membranes, with increasingly larger relative proportion of the hybrid polyunsaturated lipid PAPC (4:0−5:4PC) to DAPC (di5:4PC) (i.e., X H). We also calculated an elastic contribution to γ by the Lo−Ld thickness mismatch, tilt moduli, and bending moduli, as predicted by theory. We found that an increase in X H decreased the overall γ value and the elastic contribution to line tension. The effect on the elastic line tension is driven by a reduced hydrophobic mismatch. Changes in the elastic constants of the phases due to an increase in X H produced a slightly larger elastic γ term. In addition to this elastic energy, other major contributions to γ are found in these model membranes. Increasing X H decreases both elastic and nonelastic contributions to γ. Finally, PAPC also behaves as a linactant, relaxing γ through an interfacial effect, as predicted by theoretical results. This study gives insight into the actual contribution of distinct energy terms to γ in bilayers containing polyunsaturated hybrid lipids.

The Journal of chemical physics, Jan 21, 2014

The coupling between local composition fluctuations in binary lipid membranes and curvature affec... more The coupling between local composition fluctuations in binary lipid membranes and curvature affects the lateral membrane structure. We propose an efficient method to compute the composition-curvature coupling in molecular simulations and apply it to two coarse-grained membrane models-a minimal, implicit-solvent model and the MARTINI model. Both the weak-curvature behavior that is typical for thermal fluctuations of planar bilayer membranes as well as the strong-curvature regime corresponding to narrow cylindrical membrane tubes are studied by molecular dynamics simulation. The simulation results are analyzed by using a phenomenological model of the thermodynamics of curved, mixed bilayer membranes that accounts for the change of the monolayer area upon bending. Additionally the role of thermodynamic characteristics such as the incompatibility between the two lipid species and asymmetry of composition are investigated.

The Journal of Physical Chemistry B, 2011

The Journal of Physical Chemistry B, 2012

We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an uns... more We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an unsaturated lipid, and a fully saturated lipid, by means of molecular dynamics simulations of the MARTINI coarse grain model. We aimed at comparing lateral organization and local properties of bilayers containing phosphatidylcholine (PC) lipids, either with two unsaturated tails (symmetric), or one unsaturated and one saturated tail (asymmetric), as the low-melting component of the mixture. The number of unsaturations per chain was systematically varied in both classes of unsaturated lipids, to account for its consequences in segregation. In the asymmetric unsaturated PCs, the saturated tail was kept identical to the hydrophobic chains of the fully saturated lipid component. Membranes with a symmetric or an asymmetric unsaturated lipid, with the same kind of unsaturated chain, show different phase behavior. Symmetric polyunsaturated PCs set the separation in two phases. Instead, the asymmetric polyunsaturated lipids induced nonideal mixing of components in single-phase bilayers. A significative drop of temperature, within the accessible temperature range, enhances the segregation in mixtures with the more unsaturated asymmetric PC, but still within a single phase. This different phase behavior between membranes with symmetric and asymmetric unsaturated PCs is also observed for lipids with the same total number of unsaturations. On the other hand, the degree of unsaturation per se enhances the segregation, by increasing the composition fluctuations in single-phase membranes with asymmetric PC lipids, and raising the line tension in the two-phase bilayer mixtures with symmetric polyunsaturated PCs. Dynamic clusters of unsaturated asymmetric lipids can be identified. The clusters show no correlation between leaflets, as observed for the phase domains in mixtures with the symmetric polyunsaturated PCs. Interestingly, we found that asymmetric PC lipids have a preferential orientation such that their saturated tails increase their density toward the periphery of the clusters, facing regions enriched in the fully saturated lipids and cholesterol. The degree of unsaturation increases the cluster size and also enhances the anisotropy of the orientation. The surface density of cholesterol follows a gradient that favors its interaction with the saturated tails. Such gradients in composition lead to gradients in order parameters, such as the conformational order and the area of the tails, which increases away from the unsaturated lipid clusters. We compared, in addition, differences in hydrophobic length mismatch between acyl chains of the low-melting and high-melting components, in mixtures containing either symmetric or asymmetric unsaturated lipids.

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2005

Solvent solubilized myelin membranes spread as monomolecular layers at the air-water interface sh... more Solvent solubilized myelin membranes spread as monomolecular layers at the air-water interface show a heterogeneous pattern at all surface pressures. In order to asses the role of myelin protein and lipid components in the surface structuring we compared the topography, as seen by Brewster angle microscopy (BAM) and epifluorescence microscopy, of monolayers made from mixtures containing all myelin lipids (except gangliosides) and variable proportions of Folch-Lees proteolipid protein (PLP, the major protein component of myelin). The presence of the single PLP, in the absence of the other myelin proteins, can reproduce the surface pattern of the whole myelin extract films in a concentration-dependant manner. Moreover, a threshold mole fraction of PLP is necessary to induce the lipid-protein component reorganization leading to the appearance of a rigid (gray) phase, acting as a surface skeleton, at low surface pressures and of fractal clusters at high surface pressures. The average size of those clusters is also dependent on the PLP content in the monolayer and on the time elapsed from the moment of film spreading, as they apparently result from an irreversible lateral aggregation process. The transverse rearrangement of the monolayer occurring under compression was different in films with the highest and lowest PLP mole fractions tested.

Langmuir, 2003

In this paper we report the dynamic response of the lateral topography and reflectance of monolay... more In this paper we report the dynamic response of the lateral topography and reflectance of monolayers of glycosphingolipids under changes of surface pressure (π) and composition. Epifluorescence and Brewster angle microscopy (BAM) observations have been carried out on pure monolayers formed with ceramide (Cer) and a series of glycosphingolipids (galactocerebroside, GM1 ganglioside, and asialo-GM1), and on mixed films formed with Cer and GM1. The curves of reflectance versus π for films of pure components are very dependent on the type and length of the oligosaccharide chain in the polar headgroup and are in agreement with the phase state of the π-area isotherms and with the overall molecular reorientation under compression shown by the variation of the perpendicular resultant dipole moments. In turn, the surface appearance of films formed with mixtures of GM1 and Cer is homogeneous as assessed by BAM, but epifluorescence microscopy reveals the coexistence of expanded and condensed phase domains that are under the limit of resolution of our BAM. The addition of Cer, which has a small headgroup, to GM1, which has the largest headgroup among the lipids studied, produced an average decrease of the dependence of reflectance on π (dI/dπ). Also, we analyzed the changes of reflectance and of dI/dπ with respect to the proportion of fluorescent and nonfluorescent phases. On the basis of these data it appears that the incorporation of GM1 in the Cer-enriched phase induces a drastic increase of reflectance without marked changes of dI/dπ with respect to phases of pure Cer. Cer incorporated into GM1-enriched phases of the mixed monolayers does not affect markedly the optical properties (reflectance and dI/dπ values) compared to films of pure GM1.

Journal of Physical Chemistry B, Feb 10, 2017

Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was pr... more Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was proposed that hybrid lipids, with mixed saturated and unsaturated acyl chains, participate in the relaxation of γ through different mechanisms. In this work, we used molecular dynamics simulations of the coarse-grained MARTINI model to measure γ in liquid-ordered−liquid-disordered (Lo−Ld) membranes, with increasingly larger relative proportion of the hybrid polyunsaturated lipid PAPC (4:0−5:4PC) to DAPC (di5:4PC) (i.e., X H). We also calculated an elastic contribution to γ by the Lo−Ld thickness mismatch, tilt moduli, and bending moduli, as predicted by theory. We found that an increase in X H decreased the overall γ value and the elastic contribution to line tension. The effect on the elastic line tension is driven by a reduced hydrophobic mismatch. Changes in the elastic constants of the phases due to an increase in X H produced a slightly larger elastic γ term. In addition to this elastic energy, other major contributions to γ are found in these model membranes. Increasing X H decreases both elastic and nonelastic contributions to γ. Finally, PAPC also behaves as a linactant, relaxing γ through an interfacial effect, as predicted by theoretical results. This study gives insight into the actual contribution of distinct energy terms to γ in bilayers containing polyunsaturated hybrid lipids.

Journal of Physical Chemistry B, Mar 9, 2012

We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an uns... more We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an unsaturated lipid, and a fully saturated lipid, by means of molecular dynamics simulations of the MARTINI coarse grain model. We aimed at comparing lateral organization and local properties of bilayers containing phosphatidylcholine (PC) lipids, either with two unsaturated tails (symmetric), or one unsaturated and one saturated tail (asymmetric), as the low-melting component of the mixture. The number of unsaturations per chain was systematically varied in both classes of unsaturated lipids, to account for its consequences in segregation. In the asymmetric unsaturated PCs, the saturated tail was kept identical to the hydrophobic chains of the fully saturated lipid component. Membranes with a symmetric or an asymmetric unsaturated lipid, with the same kind of unsaturated chain, show different phase behavior. Symmetric polyunsaturated PCs set the separation in two phases. Instead, the asymmetric polyunsaturated lipids induced nonideal mixing of components in single-phase bilayers. A significative drop of temperature, within the accessible temperature range, enhances the segregation in mixtures with the more unsaturated asymmetric PC, but still within a single phase. This different phase behavior between membranes with symmetric and asymmetric unsaturated PCs is also observed for lipids with the same total number of unsaturations. On the other hand, the degree of unsaturation per se enhances the segregation, by increasing the composition fluctuations in single-phase membranes with asymmetric PC lipids, and raising the line tension in the two-phase bilayer mixtures with symmetric polyunsaturated PCs. Dynamic clusters of unsaturated asymmetric lipids can be identified. The clusters show no correlation between leaflets, as observed for the phase domains in mixtures with the symmetric polyunsaturated PCs. Interestingly, we found that asymmetric PC lipids have a preferential orientation such that their saturated tails increase their density toward the periphery of the clusters, facing regions enriched in the fully saturated lipids and cholesterol. The degree of unsaturation increases the cluster size and also enhances the anisotropy of the orientation. The surface density of cholesterol follows a gradient that favors its interaction with the saturated tails. Such gradients in composition lead to gradients in order parameters, such as the conformational order and the area of the tails, which increases away from the unsaturated lipid clusters. We compared, in addition, differences in hydrophobic length mismatch between acyl chains of the low-melting and high-melting components, in mixtures containing either symmetric or asymmetric unsaturated lipids.

Journal of Physical Chemistry B, Dec 28, 2010

The Journal of Physical Chemistry B, 2017

Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was pr... more Line tension (γ) is a key parameter for the structure and dynamics of membrane domains. It was proposed that hybrid lipids, with mixed saturated and unsaturated acyl chains, participate in the relaxation of γ through different mechanisms. In this work, we used molecular dynamics simulations of the coarse-grained MARTINI model to measure γ in liquid-ordered−liquid-disordered (Lo−Ld) membranes, with increasingly larger relative proportion of the hybrid polyunsaturated lipid PAPC (4:0−5:4PC) to DAPC (di5:4PC) (i.e., X H). We also calculated an elastic contribution to γ by the Lo−Ld thickness mismatch, tilt moduli, and bending moduli, as predicted by theory. We found that an increase in X H decreased the overall γ value and the elastic contribution to line tension. The effect on the elastic line tension is driven by a reduced hydrophobic mismatch. Changes in the elastic constants of the phases due to an increase in X H produced a slightly larger elastic γ term. In addition to this elastic energy, other major contributions to γ are found in these model membranes. Increasing X H decreases both elastic and nonelastic contributions to γ. Finally, PAPC also behaves as a linactant, relaxing γ through an interfacial effect, as predicted by theoretical results. This study gives insight into the actual contribution of distinct energy terms to γ in bilayers containing polyunsaturated hybrid lipids.

The Journal of chemical physics, Jan 21, 2014

The coupling between local composition fluctuations in binary lipid membranes and curvature affec... more The coupling between local composition fluctuations in binary lipid membranes and curvature affects the lateral membrane structure. We propose an efficient method to compute the composition-curvature coupling in molecular simulations and apply it to two coarse-grained membrane models-a minimal, implicit-solvent model and the MARTINI model. Both the weak-curvature behavior that is typical for thermal fluctuations of planar bilayer membranes as well as the strong-curvature regime corresponding to narrow cylindrical membrane tubes are studied by molecular dynamics simulation. The simulation results are analyzed by using a phenomenological model of the thermodynamics of curved, mixed bilayer membranes that accounts for the change of the monolayer area upon bending. Additionally the role of thermodynamic characteristics such as the incompatibility between the two lipid species and asymmetry of composition are investigated.

The Journal of Physical Chemistry B, 2011

The Journal of Physical Chemistry B, 2012

We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an uns... more We studied the phase behavior of various ternary bilayer mixtures composed of cholesterol, an unsaturated lipid, and a fully saturated lipid, by means of molecular dynamics simulations of the MARTINI coarse grain model. We aimed at comparing lateral organization and local properties of bilayers containing phosphatidylcholine (PC) lipids, either with two unsaturated tails (symmetric), or one unsaturated and one saturated tail (asymmetric), as the low-melting component of the mixture. The number of unsaturations per chain was systematically varied in both classes of unsaturated lipids, to account for its consequences in segregation. In the asymmetric unsaturated PCs, the saturated tail was kept identical to the hydrophobic chains of the fully saturated lipid component. Membranes with a symmetric or an asymmetric unsaturated lipid, with the same kind of unsaturated chain, show different phase behavior. Symmetric polyunsaturated PCs set the separation in two phases. Instead, the asymmetric polyunsaturated lipids induced nonideal mixing of components in single-phase bilayers. A significative drop of temperature, within the accessible temperature range, enhances the segregation in mixtures with the more unsaturated asymmetric PC, but still within a single phase. This different phase behavior between membranes with symmetric and asymmetric unsaturated PCs is also observed for lipids with the same total number of unsaturations. On the other hand, the degree of unsaturation per se enhances the segregation, by increasing the composition fluctuations in single-phase membranes with asymmetric PC lipids, and raising the line tension in the two-phase bilayer mixtures with symmetric polyunsaturated PCs. Dynamic clusters of unsaturated asymmetric lipids can be identified. The clusters show no correlation between leaflets, as observed for the phase domains in mixtures with the symmetric polyunsaturated PCs. Interestingly, we found that asymmetric PC lipids have a preferential orientation such that their saturated tails increase their density toward the periphery of the clusters, facing regions enriched in the fully saturated lipids and cholesterol. The degree of unsaturation increases the cluster size and also enhances the anisotropy of the orientation. The surface density of cholesterol follows a gradient that favors its interaction with the saturated tails. Such gradients in composition lead to gradients in order parameters, such as the conformational order and the area of the tails, which increases away from the unsaturated lipid clusters. We compared, in addition, differences in hydrophobic length mismatch between acyl chains of the low-melting and high-melting components, in mixtures containing either symmetric or asymmetric unsaturated lipids.

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2005

Solvent solubilized myelin membranes spread as monomolecular layers at the air-water interface sh... more Solvent solubilized myelin membranes spread as monomolecular layers at the air-water interface show a heterogeneous pattern at all surface pressures. In order to asses the role of myelin protein and lipid components in the surface structuring we compared the topography, as seen by Brewster angle microscopy (BAM) and epifluorescence microscopy, of monolayers made from mixtures containing all myelin lipids (except gangliosides) and variable proportions of Folch-Lees proteolipid protein (PLP, the major protein component of myelin). The presence of the single PLP, in the absence of the other myelin proteins, can reproduce the surface pattern of the whole myelin extract films in a concentration-dependant manner. Moreover, a threshold mole fraction of PLP is necessary to induce the lipid-protein component reorganization leading to the appearance of a rigid (gray) phase, acting as a surface skeleton, at low surface pressures and of fractal clusters at high surface pressures. The average size of those clusters is also dependent on the PLP content in the monolayer and on the time elapsed from the moment of film spreading, as they apparently result from an irreversible lateral aggregation process. The transverse rearrangement of the monolayer occurring under compression was different in films with the highest and lowest PLP mole fractions tested.

Langmuir, 2003

In this paper we report the dynamic response of the lateral topography and reflectance of monolay... more In this paper we report the dynamic response of the lateral topography and reflectance of monolayers of glycosphingolipids under changes of surface pressure (π) and composition. Epifluorescence and Brewster angle microscopy (BAM) observations have been carried out on pure monolayers formed with ceramide (Cer) and a series of glycosphingolipids (galactocerebroside, GM1 ganglioside, and asialo-GM1), and on mixed films formed with Cer and GM1. The curves of reflectance versus π for films of pure components are very dependent on the type and length of the oligosaccharide chain in the polar headgroup and are in agreement with the phase state of the π-area isotherms and with the overall molecular reorientation under compression shown by the variation of the perpendicular resultant dipole moments. In turn, the surface appearance of films formed with mixtures of GM1 and Cer is homogeneous as assessed by BAM, but epifluorescence microscopy reveals the coexistence of expanded and condensed phase domains that are under the limit of resolution of our BAM. The addition of Cer, which has a small headgroup, to GM1, which has the largest headgroup among the lipids studied, produced an average decrease of the dependence of reflectance on π (dI/dπ). Also, we analyzed the changes of reflectance and of dI/dπ with respect to the proportion of fluorescent and nonfluorescent phases. On the basis of these data it appears that the incorporation of GM1 in the Cer-enriched phase induces a drastic increase of reflectance without marked changes of dI/dπ with respect to phases of pure Cer. Cer incorporated into GM1-enriched phases of the mixed monolayers does not affect markedly the optical properties (reflectance and dI/dπ values) compared to films of pure GM1.