Interactions between cyclic cell penetrating peptides and lipid membranes

Cyclic peptides exhibit strong enhancement in receptor-binding affinity, specificity, and stability relative to their linear counterparts, partially due to their reduced conformational freedom. In this work, we examine cyclic versions of cell penetrating peptides. Using small-angle x-ray scattering (SAXS) measurements, we show that cyclic polyarginine peptides generate saddle-splay curvature more efficiently than their linear counterparts, We show how this increase in induced saddle splay curvature impinges on the efficiency of cell penetration in a series of giant vesicle and intracellular trafficking experiments.