Direct Translocation Mechanism in the Internalization of Arginine-Rich Cell-Penetrating Peptides

Arginine-rich CPPs (cell-penetrating peptides) are a series of short peptides that can be effectively internalized into cells. They are widely used as carriers of bioactive molecules. The internalization mechanisms of arginine-rich CPPs can be divided into at least two types: endocytic pathway and direct translocation. Directly translocation of internalization is limited in the local area of membrane nucleation zones. Arginine-rich CPPs interact with counteranions in the plasma membrane to induce dynamic alterations in membrane structures such as particle and transient porosity formation, local membrane inversion, changing of membrane curvature, transient void formation, and loosening of the lipid packing driven by membrane potential. In addition, counteranions pyrenebutyrate can effectively facilitate the direct translocation of arginine-rich CPPs. Concentration of CPPs, characters of the transported molecules, cultivation temperature, lipid composition of plasma membrane, cell line type, and cell oxidation state can all influence even determine the internalization mechanism of arginine-rich CPPs. Cell-specific CPPs may address the poor targeting of CPPs.

CSTR: 32200.14.cjcb.2020.09.0027