Inward Budding and Endocytosis of Membranes Regulated by de Novo Designed Peptides

Protein-mediated endocytosis of membrane is a key event in biological system. The mechanism, however, is still not clear. Using a de novo designed bola-type peptide KKKLLLLLLLLKKK (K₃L₈K₃) as a protein mimic, we studied how it induced giant unilamellar vesicle (GUV) to form inward buds or endocytosis at varying conditions. Results show that the inward budding is initiated as the charged lipids are neutralized by K₃L₈K₃, which results in a negative spontaneous curvature. If the charged lipids have unsaturated tails, the buddings are slim fibrils, which can further wrap into a spherical structure. In the case of saturated charged lipids, the buddings are rigid tubules, stable in the studied time period. The unsaturated lipid to saturated lipid ratio in the mother membrane is another key parameter governing the shape and dynamics of the buds. A complete endocytosis is observed when K₃L₈K₃ is attached with a hydrophobic moiety, suggesting that hydrophobic interaction helps the buds to detach from the mother membrane. The molecules in the surrounding medium, such as negatively charged oligonucleotides, are engulfed into the GUV via endocytosis pathway induced by K₃L₈K₃. Our study provides a novel strategy for illustrating the endocytosis mechanism by using peptides of simple sequence.