ION-TRANSPORT AND SELECTIVITY IN MODEL LIPID-MEMBRANES CARRYING INCORPORATED CYTOLYTIC PROTEIN TOXINS

We used artificial planar lipid membranes to investigate the mode of action of cytolysins of different origin. We studied some pathologically important bacterial toxins(e.g. S. aureus alpha-toxin,C. perfringens THETA-toxin, B. thuringiensis delta-endotoxin and E. coli alpha-hemolysin). All these toxins are used by the bacteria to damage the cells of the invaded organism. We also studied cytolysins of animal origin which are used to react against the attack of foreign organisms like cytolysins from the nematocysts of sea anemones. These proteins disrupt the permeability barrier of the attacked cell membrane by opening a pore into the lipid matrix. We found that in most cases a receptor is not truly required to render them competent to bind to a cell membrane, they spontaneously insert into preformed pure lipid membranes. Several properties of the resulting pores were compared. They are generally large, water filled, and stay open for long periods. In most cases neutral molecules up to a few kDa molecular weight (like sugars and metabolites) can easily pass through the channel. They are weakly selective, usually being able to discriminate only between anions and cations. The selectivity depends on the presence of fixed charges on the protein since it is modulated by pH and by chemical modification of the protein charged residues.