Τίτλος:
Vinblastine: cholesterol interactions in lipid bilayers
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The anti-mitotic character of vinblastine (VLBS) may relate to its lipophilic nature leading to its hydrophobic interaction with proteins or to its perturbation in lipid bilayers that decreases the lipid fluidity. For these VLBS actions, our work focused on the effects of vinblastine in lipid bilayers. Our aim is to highlight the effects of this highly lipophilic vinca molecule in lipid bilayers in an attempt to use this information in the future for its delivery in liposomal systems avoiding some of its detrimental side effects. Thus, a combination of Differential Scanning Calorimetry (DSC), Raman spectroscopy, X-ray diffraction and Molecular Dynamics (MD) has been applied to study the interactions of antineoplastic VLBS in lipid bilayers. VLBS appears to be distributed to the hydrophilic and hydrophobic segments of lipid bilayers. When cholesterol (CHL) is present in the membrane, VLBS associates not only with the hydrophilic and hydrophobic segments, but also with CHL. This results in the interference of their dynamic effects and causes an antagonistic influence. Thus, in a real biological environment, the interaction between VLBS molecules and cholesterol-rich domains may be disfavored, and a VLBS–CHL separation may occur. Additionally, in our simulations VLBS molecules that were initially placed in the water layer spontaneously entered the lipid bilayer and incorporated into the outer part of the membrane. Finally, we predict that the presence of VLBS favors interdigitation of membrane's alkyl chains. © 2019 Elsevier Inc.
Συγγραφείς:
Leonis, G.
Semidalas, E.C.
Chatzigeorgiou, P.
Pollatos, E.
Semidalas, C.E.
Rappolt, M.
Viras, K.
Mavromoustakos, T.
Περιοδικό:
Advances in Biomembranes and Lipid Self-Assembly
DOI:
10.1016/bs.abl.2019.01.008
