Steric interactions between mobile ligands facilitate complete wrapping in passive endocytosis

TL;DR

This study uses theory and simulations to show that steric interactions among mobile ligands on particles facilitate complete wrapping during passive endocytosis, informing better design of drug delivery systems.

Contribution

It reveals how ligand mobility and steric interactions influence membrane wrapping, offering new insights into endocytosis mechanisms and vector design.

Findings

Steric interactions among ligands enhance wrapping efficiency.

Mobile, non-interacting ligands hinder complete wrapping.

Structural ligand details affect endocytosis efficiency.

Abstract

Receptor-mediated endocytosis is an ubiquitous process through which cells internalize biological or synthetic nanoscale objects, including viruses, unicellular parasites, and nanomedical vectors for drug or gene delivery. In passive endocytosis the cell plasma membrane wraps around the "invader" particle driven by ligand-receptor complexation. By means of theory and numerical simulations, here we demonstrate how particles decorated by freely diffusing and non-mutually-interacting (ideal) ligands are significantly more difficult to wrap than those where ligands are either immobile or interact sterically with each other. Our model rationalizes the relationship between uptake mechanism and structural details of the invader, such as ligand size, mobility and ligand/receptor affinity, providing a comprehensive picture of pathogen endocytosis and helping the rational design of efficient drug delivery vectors.