Interplay of Nanoparticle Rigidity and Its Translocation Ability through Cell Membrane

Understanding the endocytic process of nanoparticles (NPs) with different mechanical rigidity by cell membranes is critical to the development of effective drug delivery vectors as well as their nanotoxicity. Here we perform experiments, coarse-grained molecular dynamics simulations and theoretical analysis to investigate the role of NPs’ mechanical rigidity on their cellular endocytic process. Experiments based on two types of engineered Au NPs with the similar properties but different rigidities are synthesized to investigate their cellular uptake efficiency and find that rigider NPs can achieve a higher cellular uptake efficiency. Simulation results confirm that rigid NPs can achieve a full wrapping by forming a double-layer coated endosome while relatively soft NPs can only reach, at maximum, 40% surface coverage by membrane lipids. Simulation results also capture an intriguing translocation of multiple NPs with different rigidities in a cooperative manner where NPs’ mechanical rigidities regulates th...