Simple Model of the Transduction of Cell-Penetrating Peptides

TL;DR

This paper proposes a simple capacitor-based model explaining how cell-penetrating peptides transduce across cell membranes, aligning with experimental data and offering testable predictions for the mechanism.

Contribution

It introduces a novel, simple biophysical model of CPP transduction involving capacitor-like membrane interactions, advancing understanding of peptide entry mechanisms.

Findings

Model aligns with experimental data on oligoarginine transduction

Predicts transient pore formation via electroporation

Offers three testable hypotheses about CPP transduction

Abstract

Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically useful when fused to well-chosen chains of fewer than about 35 amino acids. I offer a simple model of transduction in which phosphatidylserines and CPPs effectively form two plates of a capacitor with a voltage sufficient to cause the formation of transient pores (electroporation). The model is consistent with experimental data on the transduction of oligoarginine into mouse C2-C12 myoblasts and makes three testable predictions.