Competitive Binding to Lipid Bilayers by Peptides and Drugs

Abstract

The lipid matrix of cell membrane is a natural binding site for amphipathic molecules including drugs, peptides and proteins. In this report we investigate how two different binding molecules might interfere with each other. Specifically we studied how an amphipathic drug, curcumin, influenced the interaction between peptides and lipid bilayers. Magainin is a well-known antimicrobial peptide. Previous studies showed that magainin binds to lipid bilayers and induce pores in the membrane when and only when P/L exceeds a critical value. This is demonstrated by a GUV exposed to 10 uM magainin. The initial binding of magainin expanded the GUV area to a maximum dA/A when P/L reached the critical value, then the pores appeared. However, if a GUV was exposed to 10 uM curcumin first and then to 10 uM magainin, the GUV first expanded its area by curcumin binding. The subsequent exposure to magainin only slightly expanded the GUV area without inducing any pore formation. We then studied the competition between curcumin and penetratin. Penetratin binds to a lipid bilayer as an alpha-helix up to a critical value P/L∗. However, when P/L exceeds P/L∗, penetratin aggregates to beta-form. This was demonstrated by a GUV exposed to penetratin solution. The GUV first expanded its area due to penetratin binding. After the area expansion matched the value corresponding to P/L=P/L∗, the beta aggregates started to appear on the surface of GUV.The effect of curcumin binding to penetratin is different from to magainin. When a curcumin bound GUV was introduced to a solution containing 20μM penetratin, the protrusion length did’t significantly increase before it decreased. The results can be interpreted as penetratin partially replaced curcumin bound on the membrane, and the initially bound curcumin appeared to accelerate the beta-aggregate formation of penetratin.