Tuning the Response of a pH-Sensitive Membrane Switch

摘要

To extend the versatility of the PEAA system, we have modified the critical pH for the onset of membrane destabiliza-tion. This has been achieved by copolymerizing 2-ethylacrylic acid (EAA) with methacrylic acid (MAA) to obtain copolymers of varying composition. That these copolymers would show behavior distinct from that of PEAA was anticipated on the basis of earlier work on poly(methacrylic acid), which shows no ability to solubilize lecithin membranes at any pH. In fact, increasing MAA mole fraction leads to progressive reduction in the critical pH for membrane solubilization, which can be observed turbidometrically. This allows for "tuning" of the copolymer to any desired critical pH, from pH 5.7 to 6.5. Such tuning is useful in biological applications that require targeting to different intracellular destinations, which may maintain different degrees of acidity. It is interesting to note that a variety of viral fusion proteins exhibit similar variations in their pH sensitivity, which may relate to a preferred point in the endocytic pathway for cytoplasmic entry.