Cell-Permeable Peptides Induce Remodeling Of Cell Membranes

Nathan Schmidt, Physics, UIUC

Cell-Permeable Peptides (CPPs) have the ability to translocate across the plasma membrane of live cells. To date the most widely studied CPPs have been the protein transduction domain of HIV TAT protein, and Penetratin peptide, derived from the homeodomain of Antennapedia. Although both have demonstrated the capability to transport biologically active macromolecules into cells, suggesting they have potential biotechnological applications such as intracellular drug delivery, the mechanism of cellular entry is not well understood. To better understand the interactions of TAT and Penetratin peptides with model cell membranes we used small angle X-ray scattering (SAXS). In anionic liposomes with negative intrinsic curvature, both peptides induce a bicontinuous cubic Pn3m phase with ~6 nm pores. The induced pore size is sufficient for direct translocation of many protein sized objects, and may represent an intermediate state for higher order processes such as receptor independent endocytosis.