Theoretical Study of Phospholipid Membranes: the Complex Role of Cholesterol and Lipid Unsaturation

• Autores: Héctor Martínez-Seara Monné
• Directores de la Tesis: Ramon Reigada Sanz (dir. tes.), Francesc Sagués Mestre (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2010
• Idioma: inglés
• Tribunal Calificador de la Tesis: Xavier Daura Ribera (presid.), Jaime Rubio Martínez (secret.), Marta Pasenkiewicz Gierula (voc.)
• Materias:
  • Matemáticas
    • Ciencia de los ordenadores
      • Simulación
  • Física
    • Química física
      • Fenómenos de membrana
    • Física del estado sólido
      • Interfases
• Enlaces
  • Tesis en acceso abierto en:  TDX  Dipòsit Digital de la UB 
• Resumen

  • The Doctoral dissertation titled “Theoretical Study of Phospholipid Membranes: the Complex Role of Cholesterol and Lipid Unsaturation” covers biological membrane modeling by means of molecular dynamics. The main focus of the dissertation is to study the role of phospholipid unsaturation and cholesterol in animal cell membrane properties. In general, it aims to find the molecular mechanisms underlying naturally occurring phenomena, such as the preference displayed by nature for phospholipids with an unsaturated sn-2 chain where the double bond is placed in its middle. Significant results were obtained regarding the importance of the double bond position in phospholipidic membranes. We report that lipids with a double bond in the middle of their acyl chain present the largest capacity to induce disorder in the membrane. We also found that this effect is enhanced when the unsaturated acyl chain is attached to the sn-2 lipid. Another important result obtained in this work is the explanation of the role of cholesterol as promoter of in-plane ordering due to its collective action over surrounding phospholipids. We report the natural preference of cholesterol to be placed in the second coordination shell in the membrane plane in respect to other cholesterols. In other words cholesterols do not like to be in direct contact with each other. This result strongly supports the umbrella theory. Additionally we found that cholesterols place themselves in respect to the others in a well-defined 3 fold symmetry pattern. The combination of these two features is likely responsible for the condensation effect, as the ordering of the lipid tails could be explained by their sandwiching between cholesterols. These results, never reported before, shed light on the reasons behind the natural lipid selection and the mechanism underlying the well-known ordering effects of cholesterol which are largely controversial. Final part of this Doctoral dissertation focuses on membranes that contain cardiolipins instead of cholesterol like the one present in the mitochondria.