Surface behavior and peptide –lipid interactions of the cyclic neuropeptide melanin concentrating hormone (MCH).

VARAS MARIANA; SANCHEZ JULIETA; SANCHEZ MARIELA; RUBIALES DE BARIOGLIO, SUSANA ELIZABETH; PERILO MARIA

J Phys Chem B

Año: 2009 vol. 112 p. 7330 - 7337

1520-6106

The kinetics and the thermodynamics of melanin concentrating hormone (MCH) adsorption, penetration, and mixing with membrane components are reported. MCH behaved as a surface active peptide, forming stable monolayers at a lipid-free air-water interface, with an equilibrium spreading pressure, a collapse pressure, and a minimal molecular area of 11 mN/m, 13 mN/m, and 140 Å2, respectively. Additional peptide interfacial stabilization was achieved in the presence of lipids, as evidenced by the expansion observed at π > πsp in monolayers containing premixtures of MCH with zwitterionic or charged lipids. The MCH-monolayer association and dissociation rate constants were 9.52 × 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors-water interface, with an equilibrium spreading pressure, a collapse pressure, and a minimal molecular area of 11 mN/m, 13 mN/m, and 140 Å2, respectively. Additional peptide interfacial stabilization was achieved in the presence of lipids, as evidenced by the expansion observed at π > πsp in monolayers containing premixtures of MCH with zwitterionic or charged lipids. The MCH-monolayer association and dissociation rate constants were 9.52 × 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors2, respectively. Additional peptide interfacial stabilization was achieved in the presence of lipids, as evidenced by the expansion observed at π > πsp in monolayers containing premixtures of MCH with zwitterionic or charged lipids. The MCH-monolayer association and dissociation rate constants were 9.52 × 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptorsπ > πsp in monolayers containing premixtures of MCH with zwitterionic or charged lipids. The MCH-monolayer association and dissociation rate constants were 9.52 × 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors-monolayer association and dissociation rate constants were 9.52 × 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors× 10-4 μM-1 min-1 and 8.83 × 10-4 min-1, respectively. The binding of MCH to the dpPC-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors-water interface had a Kd ) 930 nM at 10 mN/m. MCH penetration in lipid monolayers occurred even up to πcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptorsπcutoff ) 29-32 mN/m. The interaction stability, binding orientation, and miscibility of MCH in monolayers depended on the lipid type, the MCH molar fraction in the mixture, and the molecular packing of the monolayer. This predicted its heterogeneous distribution between different self-separated membrane domains. Our results demonstrated the ability of MCH to incorporate itself into biomembranes and supports the possibility that MCH affects the activity of mechanosensitive membrane proteins through mechanisms unrelated with binding to specific receptors