Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
Abstract:
The interactions between membrane proteins and cell membranes are critical in many life processes. Giant unilamellar vesicles (GUVs) and peptides are simple but effective models of membranes and membrane proteins, respectively. Here, we designed four peptides composed of lysine (K) and leucine (L) amino acids, K14, (KL2KL2K)2, (KL2KL3)2, and K6L8, and examined their interactions with neutral and negatively charged GUVs. The peptide K14 has the largest charge density and is able to coat the GUV surface without damaging its structure. Whereas, leakage is observed in both neutral and charged GUVs in the presence of (KL2KL2K)2 and (KL2KL3)2, which can form amphiphilic α-helices in hydrophobic environments. However, the leakage rates as a function of peptide concentration are reversed for the neutral and charged GUVs. Thus, leakage occurs in two steps: absorption of peptides on the surface up to a certain level, followed by disruption of the membrane. The peptide K6L8 has the same chemical composition as (KL2KL2K)2, but induces leakage only on negatively charged GUVs, while neutral GUVs undergo outward budding. Conformational changes of GUVs induced by simple peptides can be attributed to the working location (on the surface or inside the membrane), and the strength of electrostatic and hydrophobic interactions. Overall, the results provide a better understanding of membrane protein mechanisms.
