Influence of Hydrophobic Mismatch on pHILIP Insertion Dynamics

pH-Low Insertion Peptides (pHLIPs) are peptides that insert into biological membranes under acidic environments. This feature enables them to selectively target acidic microenvironments such as tumor tissues. Hydrophobic mismatch plays a pivotal role in determining peptide orientation and insertion processes. This presentation focuses on how variations in hydrophobic mismatch modulate the insertion dynamics of peptides and the corresponding structural response of lipid membranes. The developed model highlights the significance of lipid–peptide interactions in modulating membrane behavior and provides mechanistic insight into the folding and insertion processes of pHLIPs. These findings may offer a framework for the design of membrane-active therapeutics.