TY - JOUR
T1 - Multistep Interactions between Ibuprofen and Lipid Membranes
AU - Sun, Simou
AU - Sendecki, Anne M.
AU - Pullanchery, Saranya
AU - Huang, Da
AU - Yang, Tinglu
AU - Cremer, Paul S.
N1 - Funding Information:
We acknowledge support from the Office of Naval Research (N00014-14-1-0792) and the National Science Foundation (CHE-1709735).
PY - 2018/9/11
Y1 - 2018/9/11
N2 - Ibuprofen (IBU) interacts with phosphatidylcholine membranes in three distinct steps as a function of concentration. In a first step (<10 μM), IBU electrostatically adsorbs to the lipid headgroups and gradually decreases the interfacial potential. This first step helps to facilitate the second step (10-300 μM), in which hydrophobic insertion of the drug occurs. The second step disrupts the packing of the lipid acyl chains and expands the area per lipid. In a final step, above 300 μM IBU, the lipid membrane begins to solubilize, resulting in a detergent-like effect. The results described herein were obtained by a combination of fluorescence binding assays, vibrational sum frequency spectroscopy, and Langmuir monolayer compression experiments. By introducing trimethylammonium-propane, phosphatidylglycerol, and phosphatidylethanolamine lipids as well as cholesterol, we demonstrated that both the chemistry of the lipid headgroups and the packing of lipid acyl chains can substantially influence the interactions between IBU and the membranes. Moreover, different membrane chemistries can alter particular steps in the binding interaction.
AB - Ibuprofen (IBU) interacts with phosphatidylcholine membranes in three distinct steps as a function of concentration. In a first step (<10 μM), IBU electrostatically adsorbs to the lipid headgroups and gradually decreases the interfacial potential. This first step helps to facilitate the second step (10-300 μM), in which hydrophobic insertion of the drug occurs. The second step disrupts the packing of the lipid acyl chains and expands the area per lipid. In a final step, above 300 μM IBU, the lipid membrane begins to solubilize, resulting in a detergent-like effect. The results described herein were obtained by a combination of fluorescence binding assays, vibrational sum frequency spectroscopy, and Langmuir monolayer compression experiments. By introducing trimethylammonium-propane, phosphatidylglycerol, and phosphatidylethanolamine lipids as well as cholesterol, we demonstrated that both the chemistry of the lipid headgroups and the packing of lipid acyl chains can substantially influence the interactions between IBU and the membranes. Moreover, different membrane chemistries can alter particular steps in the binding interaction.
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U2 - 10.1021/acs.langmuir.8b01878
DO - 10.1021/acs.langmuir.8b01878
M3 - Article
C2 - 30148644
AN - SCOPUS:85053016957
VL - 34
SP - 10782
EP - 10792
JO - Langmuir
JF - Langmuir
SN - 0743-7463
IS - 36
ER -