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Intermolecular interaction of phosphatidylinositol with the lipid raft molecules sphingomyelin and cholesterol

View Article: PubMed Central - PubMed

ABSTRACT

Diacylphosphatidylinositol (PI) is the starting reactant in the process of phosphatidylinositide-related signal transduction mediated through the lipid raft domain. We investigated intermolecular interactions of PI with major raft components, sphingomyelin (SM) and cholesterol (Chol), using surface pressure–molecular area (π–A) isotherm measurements. The classical mean molecular area versus composition plot showed that the measured mean molecular areas are smaller in PI/Chol mixed monolayers and larger in PI/SM mixed monolayers than those calculated on the basis of the ideal additivity. These results indicate that PI interacts attractively with Chol and repulsively with SM. In addition, we energetically evaluated the interaction of PI with SM/Chol mixtures and found that the mixing energy of PI/SM/Chol ternary monolayers decreased as the molar ratio of Chol to SM increased. In order to quantitatively analyze the distribution of PI we calculated the chemical potentials of mixing of PI into the SM/Chol mixed monolayer and into the dioleoylphosphatidylcholine (DOPC) monolayer, which was used as a model for the fluid matrix, on the basis of partial molecular area analysis. Analysis using the chemical potential of mixing of PI suggested that partition of PI molecules between these two monolayers can be changed by a factor of about 1.7 in response to change in Chol molar fraction in the SM/Chol mixed monolayer from 0.3 to 0.6 when the concentration of PI in the DOPC monolayer is kept constant at 7 mol%.

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Chemical potential of mixing of PI into the SCm with a fixed rChol-value (ΔμPISCm) and into the DOPC monolayer (ΔμPIDOPC) as a function of XPI. As shown in equation (10), ΔμPI consists of the ideal term and the integration of ΔAPI over the surface pressure (π=0–30 mN/m). The molar ratios of Chol in the SCm, rChol, are 0 (filled inverted triangle), 0.3 (filled square), 0.6 (filled circle), 0.9 (filled diamond) and 1.0 (filled triangle). The open stars correspond to ΔμPIDOPC. Note that ΔμPISCm (rChol= 0.6) at XPI= 0.12 (arrow b) equals to ΔμPIDOPC at XPI= 0.07 (arrow a). See text for details.
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f6-4_1: Chemical potential of mixing of PI into the SCm with a fixed rChol-value (ΔμPISCm) and into the DOPC monolayer (ΔμPIDOPC) as a function of XPI. As shown in equation (10), ΔμPI consists of the ideal term and the integration of ΔAPI over the surface pressure (π=0–30 mN/m). The molar ratios of Chol in the SCm, rChol, are 0 (filled inverted triangle), 0.3 (filled square), 0.6 (filled circle), 0.9 (filled diamond) and 1.0 (filled triangle). The open stars correspond to ΔμPIDOPC. Note that ΔμPISCm (rChol= 0.6) at XPI= 0.12 (arrow b) equals to ΔμPIDOPC at XPI= 0.07 (arrow a). See text for details.

Mentions: On the basis of deviations from ideal area additivity, we calculated the excess mixing energies of PI into the SM/Chol mixtures (SCm), ΔGexSCm, to energetically evaluate the affinity of PI to the SCm. Although the results in Figure. 4 gave an insight to the Chol-dependent change in affinity of PI to SCm, they cannot be used for estimation of partition of PI molecules into different domains. As a first step toward the quantitative estimation of PI distribution, we assumed for simplicity of calculation that PI molecules are distributed between preexisting SCm and DOPC domains which are completely immiscible and laterally separated. PI molecules added to the membrane are distributed in equilibrium as their chemical potential in the two domains is the same:(8)μPISCm=μPIDOPC,where μPISCm and μPIDOPC are the chemical potential of PI molecules in the SCm domain and the DOPC domain, respectively. We can rewrite equation (8) using the chemical potential of mixing of PI molecules, ΔμPI, i.e., the difference in chemical potential between PI molecules in the pure state and in the mixture at 30 mN/m, as(9)ΔμPISCm=ΔμPIDOPC.The mixing chemical potential can be calculated from the partial-specific area of PI, API, which is obtained by extending well-known concept of partial-specific volume according to Edholm and Nagle46. Figure 5 illustrates how to calculate the API in a mixed monolayer. At first the mean molecular area obtained as a function of XPI was fitted to a quadratic function f(XPI) for convenience of calculation. The value of API at a desired XPI is obtained as the XPI= 1 intercept of the tangent of f(XPI) at the XPI46,54. The chemical potential of mixing of PI, ΔμPI, is calculated as:(10)ΔμPI=kBTln(XPI)+∫0πΔAPIdπ,where kB is the Boltzmann constant and ΔAPI = API(XPI)–API(1). The ΔAPI is integrated over the surface pressure (π= 0–30 mN/m). It should be noted that ΔμPISCm depends on XPI and the composition of SCm (rChol). We plotted ΔμPISCm(XPI, rChol) with constant rChol as a function of XPI, together with ΔμPIDOPC(XPI) in Figure 6. All the ΔμPI increased monotonously as XPI increased. The slope is steeper in the lower XPI region due to the term of ideal mixing (first term of Eq. (10)).


Intermolecular interaction of phosphatidylinositol with the lipid raft molecules sphingomyelin and cholesterol
Chemical potential of mixing of PI into the SCm with a fixed rChol-value (ΔμPISCm) and into the DOPC monolayer (ΔμPIDOPC) as a function of XPI. As shown in equation (10), ΔμPI consists of the ideal term and the integration of ΔAPI over the surface pressure (π=0–30 mN/m). The molar ratios of Chol in the SCm, rChol, are 0 (filled inverted triangle), 0.3 (filled square), 0.6 (filled circle), 0.9 (filled diamond) and 1.0 (filled triangle). The open stars correspond to ΔμPIDOPC. Note that ΔμPISCm (rChol= 0.6) at XPI= 0.12 (arrow b) equals to ΔμPIDOPC at XPI= 0.07 (arrow a). See text for details.
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Related In: Results  -  Collection

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f6-4_1: Chemical potential of mixing of PI into the SCm with a fixed rChol-value (ΔμPISCm) and into the DOPC monolayer (ΔμPIDOPC) as a function of XPI. As shown in equation (10), ΔμPI consists of the ideal term and the integration of ΔAPI over the surface pressure (π=0–30 mN/m). The molar ratios of Chol in the SCm, rChol, are 0 (filled inverted triangle), 0.3 (filled square), 0.6 (filled circle), 0.9 (filled diamond) and 1.0 (filled triangle). The open stars correspond to ΔμPIDOPC. Note that ΔμPISCm (rChol= 0.6) at XPI= 0.12 (arrow b) equals to ΔμPIDOPC at XPI= 0.07 (arrow a). See text for details.
Mentions: On the basis of deviations from ideal area additivity, we calculated the excess mixing energies of PI into the SM/Chol mixtures (SCm), ΔGexSCm, to energetically evaluate the affinity of PI to the SCm. Although the results in Figure. 4 gave an insight to the Chol-dependent change in affinity of PI to SCm, they cannot be used for estimation of partition of PI molecules into different domains. As a first step toward the quantitative estimation of PI distribution, we assumed for simplicity of calculation that PI molecules are distributed between preexisting SCm and DOPC domains which are completely immiscible and laterally separated. PI molecules added to the membrane are distributed in equilibrium as their chemical potential in the two domains is the same:(8)μPISCm=μPIDOPC,where μPISCm and μPIDOPC are the chemical potential of PI molecules in the SCm domain and the DOPC domain, respectively. We can rewrite equation (8) using the chemical potential of mixing of PI molecules, ΔμPI, i.e., the difference in chemical potential between PI molecules in the pure state and in the mixture at 30 mN/m, as(9)ΔμPISCm=ΔμPIDOPC.The mixing chemical potential can be calculated from the partial-specific area of PI, API, which is obtained by extending well-known concept of partial-specific volume according to Edholm and Nagle46. Figure 5 illustrates how to calculate the API in a mixed monolayer. At first the mean molecular area obtained as a function of XPI was fitted to a quadratic function f(XPI) for convenience of calculation. The value of API at a desired XPI is obtained as the XPI= 1 intercept of the tangent of f(XPI) at the XPI46,54. The chemical potential of mixing of PI, ΔμPI, is calculated as:(10)ΔμPI=kBTln(XPI)+∫0πΔAPIdπ,where kB is the Boltzmann constant and ΔAPI = API(XPI)–API(1). The ΔAPI is integrated over the surface pressure (π= 0–30 mN/m). It should be noted that ΔμPISCm depends on XPI and the composition of SCm (rChol). We plotted ΔμPISCm(XPI, rChol) with constant rChol as a function of XPI, together with ΔμPIDOPC(XPI) in Figure 6. All the ΔμPI increased monotonously as XPI increased. The slope is steeper in the lower XPI region due to the term of ideal mixing (first term of Eq. (10)).

View Article: PubMed Central - PubMed

ABSTRACT

Diacylphosphatidylinositol (PI) is the starting reactant in the process of phosphatidylinositide-related signal transduction mediated through the lipid raft domain. We investigated intermolecular interactions of PI with major raft components, sphingomyelin (SM) and cholesterol (Chol), using surface pressure–molecular area (π–A) isotherm measurements. The classical mean molecular area versus composition plot showed that the measured mean molecular areas are smaller in PI/Chol mixed monolayers and larger in PI/SM mixed monolayers than those calculated on the basis of the ideal additivity. These results indicate that PI interacts attractively with Chol and repulsively with SM. In addition, we energetically evaluated the interaction of PI with SM/Chol mixtures and found that the mixing energy of PI/SM/Chol ternary monolayers decreased as the molar ratio of Chol to SM increased. In order to quantitatively analyze the distribution of PI we calculated the chemical potentials of mixing of PI into the SM/Chol mixed monolayer and into the dioleoylphosphatidylcholine (DOPC) monolayer, which was used as a model for the fluid matrix, on the basis of partial molecular area analysis. Analysis using the chemical potential of mixing of PI suggested that partition of PI molecules between these two monolayers can be changed by a factor of about 1.7 in response to change in Chol molar fraction in the SM/Chol mixed monolayer from 0.3 to 0.6 when the concentration of PI in the DOPC monolayer is kept constant at 7 mol%.

No MeSH data available.


Related in: MedlinePlus