Acetaminophen Interactions with Phospholipid Vesicles Induced Changes in Morphology and Lipid Dynamics

Area of Science:

• Biophysics
• Materials Science
• Pharmacology

Background:

• Acetaminophen (APAP) is widely used for pain and fever but has known toxic effects, particularly on the liver.
• Phosphatidylcholine, a key cell membrane component, is abundant in the liver, yet APAP's effects on pure phospholipid membranes are understudied.

Purpose of the Study:

• To investigate how acetaminophen (APAP) incorporation affects the structure, morphology, and fluidity of 1,2-di-(octadecenoyl)-sn-glycero-3-phosphocholine (DOPC) lipid vesicles.
• To quantify changes in vesicle rigidity, lipid content, and lipid tail dynamics upon APAP addition.

Main Methods:

• Synthesis of large unilamellar vesicles (LUVs) using DOPC.
• Structural characterization via dynamic light scattering, small-angle neutron and X-ray scattering (SANS, SAXS), and cryo-transmission electron microscopy (cryo-TEM).
• Investigation of membrane dynamics using neutron spin-echo (NSE) spectroscopy.

Main Results:

• APAP incorporation decreased the number of lipids per vesicle by up to 28% and reduced membrane bending rigidity by approximately 50%.
• Vesicles transitioned from spherical to irregularly shaped structures with increasing APAP concentration.
• NSE and cryo-TEM revealed altered lipid dynamics and increased lipid tail motion, indicating decreased membrane rigidity.

Conclusions:

• Acetaminophen significantly impacts phospholipid self-assembly, altering vesicle morphology and reducing membrane rigidity.
• The observed changes in lipid dynamics and increased space explored by lipid tails suggest a mechanism for APAP's membrane-associated effects.
• Further research into APAP's interaction with lipid bilayers is warranted given its widespread use and potential for toxicity.