Abstract

The interaction between cationic polypeptides and anionic lipid membranes is a fundamental process in cell biology, crucial for understanding phenomena such as cell-penetrating peptides, protein-membrane signaling, and drug delivery. This study presents a theoretical analysis investigating the **influence of ionic strength on the adsorption of polypeptides onto lipid membranes**. Specifically, we modeled the effect of varying KCl concentrations (10, 40, and 100 mM) on the surface (zeta) potential of liposomes composed of the anionic phospholipid cardiolipin, with adsorbed polylysine. A theoretical model was developed and used to approximate previously obtained experimental electrokinetic data. The model allowed for the determination of key physical parameters, including the polypeptide adsorption constant, the thickness of the adsorbed polymer layer, and the fraction of the membrane surface occupied at saturation. Our analysis reveals that the efficiency of polypeptide adsorption significantly **decreases with increasing ionic strength**. This effect is attributed to the screening of electrostatic interactions, which induces **conformational rearrangements** in the adsorbed polycations, leading to a more compact structure and a reduction in the membrane surface area available for binding. Furthermore, the model parameters indicate that the distribution of the adsorbed polypeptide shifts from a homogeneous layer to a clustered arrangement as the molecular weight of the polylysine increases. These findings provide critical theoretical insights into the electrostatic and conformational factors governing polypeptide-membrane interactions, which are essential for the rational design of peptide-based therapeutics.