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Certain short polycations, such as TAT and polyarginine, rapidly pass throughthe plasma membranes of mammalian cells by an unknown mechanism calledtransduction as well as by endocytosis and macropinocytosis. Thesecell-penetrating peptides (CPPs) promise to be medically useful when fused tobiologically active peptides. I offer a simple model in which one or more CPPsand the phosphatidylserines of the inner leaflet form a kind of capacitor witha voltage in excess of 180 mV, high enough to create a molecular electropore.The model is consistent with an empirical upper limit on the cargo peptide of40--60 amino acids and with experimental data on how the transduction of apolyarginine-fluorophore into mouse C2C12 myoblasts depends on the number ofarginines in the CPP and on the CPP concentration. The model makes threetestable predictions.

Molecular Electroporation and the Transduction of Oligoarginines