Acetaminophen Interactions with Phospholipid Vesicles Induced Changes in Morphology and Lipid Dynamics
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- Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States
- Department of Chemistry, Colorado School of Mines, Golden, Colorado 80401, United States
- Neutron Sciences Directorate, Oak Ridge National Laboratory (ORNL), P.O.B 2008, 1 Bethel Valley Road, Oak Ridge, Tennessee 37831, United States
- Department of Materials Science and Engineering and NUANCE Center, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, United States
- Center of Advanced Microstructures and Devices, Louisiana State University, 6980 Jefferson Highway, Baton Rouge, Louisiana 70806, United States
- NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899-8562, United States
- Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States, Department of Physics & Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803, United States
Acetaminophen (APAP) or paracetamol, despite its wide and common use for pain and fever symptoms, shows a variety of side effects, toxic effects, and overdose effects. The most common form of toxic effects of APAP is in the liver where phosphatidylcholine is the major component of the cell membrane with additional associated functionalities. Although this is the case, the effects of APAP on pure phospholipid membranes have been largely ignored. Here, we used 1,2-di-(octadecenoyl)-sn-glycero-3-phosphocholine (DOPC), a commonly found phospholipid in mammalian cell membranes, to synthesize large unilamellar vesicles to investigate how the incorporation of APAP changes the pure lipid vesicle structure, morphology, and fluidity at different concentrations. We used a combination of dynamic light scattering, small-angle neutron and X-ray scattering (SANS, SAXS), and cryo-TEM for structural characterization, and neutron spin-echo (NSE) spectroscopy to investigate the dynamics. We showed that the incorporation of APAP in the lipid bilayer significantly impacts the spherical phospholipid self-assembly in terms of its morphology and influences the lipid content in the bilayer, causing a decrease in bending rigidity. We observe a decrease in the number of lipids per vesicle by almost 28% (0.06 wt % APAP) and 19% (0.12 wt % APAP) compared to the pure DOPC (0 wt % APAP). Our results showed that the incorporation of APAP reduces the membrane rigidity by almost 50% and changes the spherical unilamellar vesicles into much more irregularly shaped vesicles. Although the bilayer structure did not show much change when observed by SAXS, NSE and cryo-TEM results showed the lipid dynamics change with the addition of APAP in the bilayer, which causes the overall decreased membrane rigidity. A strong effect on the lipid tail motion showed that the space explored by the lipid tails increases by a factor of 1.45 (for 0.06 wt % APAP) and 1.75 (for 0.12 wt % APAP) compared to DOPC without the drug.
- Research Organization:
- Louisiana State Univ., Baton Rouge, LA (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- EPSCoR Grant No. DE-SC0012432, DE-AC02-76SF00515; SC0012432; AC02-76SF00515; AC05-00OR22725
- OSTI ID:
- 1811357
- Alternate ID(s):
- OSTI ID: 1812722; OSTI ID: 1820777
- Journal Information:
- Langmuir, Journal Name: Langmuir Vol. 37 Journal Issue: 31; ISSN 0743-7463
- Publisher:
- American Chemical SocietyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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