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. Lastly, our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.
- Authors:
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). High Flux Isotope Reactor (HFIR); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Structural Molecular Biology (CSMB); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1253817
- Alternate Identifier(s):
- OSTI ID: 1265514
- Grant/Contract Number:
- AC02-05CH11231; AC05-00OR22725
- Resource Type:
- Published Article
- Journal Name:
- Biophysical Journal
- Additional Journal Information:
- Journal Name: Biophysical Journal Journal Volume: 108 Journal Issue: 10; Journal ID: ISSN 0006-3495
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Khadka, Nawal K., Cheng, Xiaolin, Ho, Chian Sing, Katsaras, John, and Pan, Jianjun. Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes. United States: N. p., 2015.
Web. doi:10.1016/j.bpj.2015.04.010.
Khadka, Nawal K., Cheng, Xiaolin, Ho, Chian Sing, Katsaras, John, & Pan, Jianjun. Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes. United States. https://doi.org/10.1016/j.bpj.2015.04.010
Khadka, Nawal K., Cheng, Xiaolin, Ho, Chian Sing, Katsaras, John, and Pan, Jianjun. Fri .
"Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes". United States. https://doi.org/10.1016/j.bpj.2015.04.010.
@article{osti_1253817,
title = {Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes},
author = {Khadka, Nawal K. and Cheng, Xiaolin and Ho, Chian Sing and Katsaras, John and Pan, Jianjun},
abstractNote = {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. Lastly, our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.},
doi = {10.1016/j.bpj.2015.04.010},
journal = {Biophysical Journal},
number = 10,
volume = 108,
place = {United States},
year = {Fri May 01 00:00:00 EDT 2015},
month = {Fri May 01 00:00:00 EDT 2015}
}
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