Mechanics of poly-arginine adsorption onto cell membrane by GM1 and their cluster forming: Coarse-grained molecular dynamics study

Ganglioside GM1 is a crucial glycolipid in neuronal cells, playing significant roles in various biological processes such as pathogen recognition, signal transduction, and protein sorting. Poly-arginine, widely used as a template for cell-penetrating peptides design, is highly valuable for molecular cargo delivery and information transmission. Investigating the interaction mechanisms and physicochemical principles of poly-arginine with GM1-containing cell membranes is essential for understanding the functions of specific cellular components and for developing novel drugs. In this study, we employed coarse-grained molecular dynamics simulations to explore the interaction processes between poly-arginine of varying concentrations and polymerization degrees with model membranes of human brain neuronal cells. Our findings reveal that poly-arginines preferentially adsorb onto GM1 and aggregate into clusters on the membrane, primarily driven by electrostatic interactions, which contributes to membrane stabilization. Additionally, poly-arginine shows a higher affinity for membranes with elevated GM1 concentrations, highlighting its potential for targeting specific membrane compositions. These insights are crucial for designing molecular targets and understanding the biophysical mechanisms in lipidomics using high-performance computational simulation methods.