40] Incorporation of toxin pores into liposomes

Abstract

Publisher Summary This chapter describes the incorporation of toxin pores into liposomes. Many cytolytic toxins primarily attack the lipid bilayer of target cells, whereby membrane damage can be affected through two basically distinct mechanisms. The first is a direct enzymatic degradation of lipids by phospholipases. Alternatively, membrane perturbation can occur through a nonenzymatic, physical derangement of the lipid bilayer, affected either through a detergent-like action of the toxin as described for mellitin, or through the insertion of the toxin molecules into the membrane with formation of transmembrane pores. Transmembrane pore formation results in free diffusion of ions and small molecules across the bilayer. If unhalted, this process ultimately leads to cellular swelling and rupture of the membrane. Pores formed by large molecular aggregates such as found with streptolysin O (SLO) may be purified by a single centrifugation of membrane detergent extracts in a sucrose density gradient. Smaller oligomers such as formed by a-toxin cannot be purified in this manner because of cosedimentation of several membrane proteins.