pH-dependent interaction of amphiphilic polypeptide poly(Lys-Aib-Leu-Aib) with lipid bilayer membrane.

A sequential polypeptide, poly(Lys-Aib-Leu-Aib) (Aib represents 2-aminoisobutyric acid), was synthesized, and the interaction with lipid membrane was studied. Poly(Lys-Aib-Leu-Aib) was designed to take an amphiphilic structure upon the formation of alpha-helix. Circular dichroism of poly(Lys-Aib-Leu-Aib) in an aqueous solution showed a negative Cotton effect due to alpha-helix. The content of alpha-helix increased when the pH was raised above 7.5 or in the presence of small unilamellar vesicles composed of egg yolk lecithin. On the other hand, alpha-helical conformation was broken by increasing the ionic strength of solution. Carboxyfluorescein leakage from dipalmitoylphosphatidylcholine (DPPC) vesicles induced by binding of poly(Lys-Aib-Leu-Aib) to the lipid membrane was facilitated in an alkaline solution and/or in a solution of low ionic strength. These phenomena can be related to the alpha-helix content of the polypeptide. It was shown that poly(Lys-Aib-Leu-Aib) induced fusion of DPPC vesicles in an alkaline solution below the phase-transition temperature of the membrane. It was further shown that the aggregation and fusion of the neutral lipid membrane was regulated by changing the pH of solution.