Mechanisms of leakage

Abstract

Two mechanisms of leakage from liposomes are discussed, (i) Cations such as Ca²⁺ induce graded release whose rate depends mainly on vesicle collisions and is associated in the case of several acidic phospholipids with fusion events. A certain degree of leakage also occurs in between collisions. Consequently, the leakage per fusion is reduced at larger lipid and Ca concentrations, (n) Certain peptides induce leakage by pore formation, which shows selectivity to the size of the entrapped molecules and occurs by an all or none mechanism; vesicles either leak or retain all of their contents. A model for final extents and kinetics of leakage due to pore forming peptides is described. This model assumes that pore forming peptides become incorporated into the vesicle bilayer and aggregate to form a pore. Recent developments in the model enable considerations of a reversible or irreversible surface aggregation of peptides. Results of final extents and kinetics of leakage induced by pore forming peptides can be well explained and predicted by this formalism. Studies demonstrate that Ca can play a dual role in affecting leakage. A case is presented where Ca ⁺ inhibits and can even arrest pore formation by a peptide, while promoting vesicle fusion. Conversely, formation of pore structures by a peptide can inhibit vesicle fusion.