title: Interactions of the anticancer drug tamoxifen with lipid membranes.
abstract: Interactions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band's magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer area compressibility modulus KA is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.
authors.affiliation: Department of Physics, University of South Florida, Tampa, Florida.
authors.forename: Nawal K
authors.initials: NK
authors.lastname: Khadka
authors.affiliation: Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Physics, University of South Florida, Tampa, Florida.
authors.forename: Chian Sing
authors.initials: CS
authors.lastname: Ho
authors.affiliation: Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, Tennessee; Department of Physics and Astronomy, University of Tennessee, Knoxville, Tennessee; Joint Institute for Neutron Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: John
authors.initials: J
authors.lastname: Katsaras
authors.affiliation: Department of Physics, University of South Florida, Tampa, Florida. Electronic address: panj@usf.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Pan
mesh_terms: D065966:Absorption, Physicochemical; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005452:Fluoresceins / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D013629:Tamoxifen / Q000494:pharmacology*; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005452:Fluoresceins; D008051:Lipid Bilayers; D053835:Unilamellar Liposomes; D013629:Tamoxifen; C007740:fluorexon