Hydrophobic Mismatching Tunes the Interaction Kinetics between α-Helical Peptides and the Cell Membrane

Hydrophobic mismatching is energetically disadvantageous for the interactions between proteins and membranes, but little is known about how hydrophobic mismatching affects the free energy of interaction and thereby tunes the interaction kinetics. Here, we use α-helical peptide KALP23 as a model and employ sum frequency generation vibrational spectroscopy (SFG-VS) to examine the influence of hydrophobic mismatching on the interaction between peptide and lipid bilayers with different hydrophobic thickness. It is found that hydrophobic mismatching has a great impact on the interaction model. The peptide inserts into the lipid bilayers when its hydrophobic length is greater than or approximately equal to the hydrophobic length of the lipid bilayer. In contrast, the peptide only partially inserts into the lipid bilayers when its hydrophobic length is much smaller than the hydrophobic length of the lipid bilayer. The increase in hydrophobic mismatching leads to excess free energy, exponentially reducing the peptide molecular number in the lipid bilayer and the transmembrane interaction rate. The picosecond scanning SFG and femtosecond broadband SFG systems do not affect the tilt angle and the relative peptide molecular number in the lipid bilayer. Our findings may improve our understanding of the mechanism of interaction between peptides and the cell membrane.