Cisplatin interaction with phosphatidylserine bilayer studied by solid-state NMR spectroscopy

Area of Science:

• Biochemistry
• Solid-state Nuclear Magnetic Resonance (NMR) Spectroscopy
• Materials Science

Background:

• Cisplatin (cis-diamminedichloridoplatinum(II)) is a cornerstone chemotherapy agent, inducing tumor cell death via platinum-DNA adducts.
• Potential mechanisms for cisplatin's side effects, including neurotoxicity and cellular resistance, may involve interactions with cellular lipids and the phospholipid bilayer.

Purpose of the Study:

• To investigate the interaction between cisplatin and phosphatidylserine (PS) lipid bilayers using advanced solid-state NMR techniques.
• To elucidate the binding sites and conformational changes occurring upon cisplatin interaction with PS bilayers.

Main Methods:

• Solid-state NMR spectroscopy, including (13)C, (31)P, and (15)N experiments, was employed.
• Rotational echo double resonance (REDOR) spectroscopy was utilized to probe distances between specific nuclei.
• 1-palmitoyl-2-oleoyl phosphatidylserine (POPS) bilayers with varying concentrations of cisplatin (10 mol% and 30 mol%) were analyzed.

Main Results:

• The study demonstrates that the serine head group of phosphatidylserine directly binds to the aquated form of cisplatin.
• Evidence suggests that cisplatin undergoes ammine ligand release upon binding to POPS.
• Further complex formation is observed, potentially involving cisplatin coordinating with oxygen atoms of the POPS phosphate group.

Conclusions:

• Cisplatin interacts with the head group of phosphatidylserine in lipid bilayers.
• The observed binding and ligand release mechanism may contribute to understanding cisplatin's cellular interactions, side effects, and resistance pathways.
• Solid-state NMR is a powerful tool for characterizing drug-lipid interactions at a molecular level.