Kinetic models for peptide-induced leakage from vesicles and cells

In this article analytical expressions for peptide-induced membrane leakage are presented. Two different models for time-dependent leakage have been developed. In the first, the leakage is assumed to be coupled by pores formed by the peptides. In the second model the peptide is assumed to induce a stress/perturbation in the membrane, and in order to reduce the stress, rearrangements in the membrane are induced. The leakage is coupled to these rearrangements, and when equilibrium is achieved no more leakage occurs. From the kinetic models simple fitting routines have been developed involving only two fitting parameters, and these have been used to fit experimental data for two prion protein-derived peptides as well as the honey bee toxin melittin in both vesicles and erythrocytes with good results. The fitted parameters provide both a quantitative and a qualitative basis for interpreting the experimental results. In addition a model for the peptide concentration-dependent leakage is presented, which was used to fit experimental data for leakage induced by the prion protein-derived peptides. The models presented in this article are compared with other models for peptide-induced membrane leakage.