Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

Nawal K. Khadka; Xiaolin Cheng; Chian Sing Ho; John Katsaras; Jianjun Pan

doi:10.1016/j.bpj.2015.04.010

Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

Nawal K. Khadka
, Xiaolin Cheng
, Chian Sing Ho
, John Katsaras
, Jianjun Pan

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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 K_A 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.

Original language	English
Pages (from-to)	2492-2501
Number of pages	10
Journal	Biophysical Journal
Volume	108
Issue number	10
DOIs	https://doi.org/10.1016/j.bpj.2015.04.010
State	Published - May 19 2015

Funding

J.P. is supported through a startup package from the University of South Florida . X.C. is partially supported by the Laboratory Directed R&D (LDRD) program at Oak Ridge National Laboratory . J.K. is supported through the Department of Energy (DOE) Scientific User Facilities Division, Office of Basic Energy Sciences . This work received additional support from the DOE Office of Biological and Environmental Research for the BioSANS instrument at the ORNL Center for Structural Molecular Biology. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under contract No. DE-AC02-05CH11231 .

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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.",

author = "Khadka, \{Nawal K.\} and Xiaolin Cheng and Ho, \{Chian Sing\} and John Katsaras and Jianjun Pan",

note = "Publisher Copyright: {\textcopyright} 2015 Biophysical Society.",

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AU - Khadka, Nawal K.

AU - Cheng, Xiaolin

AU - Ho, Chian Sing

AU - Katsaras, John

AU - Pan, Jianjun

PY - 2015/5/19

Y1 - 2015/5/19

N2 - 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.

AB - 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.

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ER -

Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

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