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Biophys J. 2015 May 19;108(10):2492-2501. doi: 10.1016/j.bpj.2015.04.010.

Interactions of the anticancer drug tamoxifen with lipid membranes.

Author information

1
Department of Physics, University of South Florida, Tampa, Florida.
2
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.
3
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.
4
Department of Physics, University of South Florida, Tampa, Florida. Electronic address: panj@usf.edu.

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.

PMID:
25992727
PMCID:
PMC4457044
DOI:
10.1016/j.bpj.2015.04.010
[Indexed for MEDLINE]
Free PMC Article

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