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Interplay of Nanoparticle Rigidity and Its Translocation Ability through Cell Membrane
Version 2 2019-10-10, 13:39
Version 1 2019-10-10, 13:08
journal contribution
posted on 2019-10-10, 13:39 authored by Liuyang Zhang, Hongmin Chen, Jin Xie, Matthew Becton, Xianqiao WangUnderstanding the endocytic process of
nanoparticles (NPs) with different mechanical rigidities is critical
to develop effective drug delivery vectors. Here, we perform experiments,
coarse-grained molecular dynamics simulations, and theoretical analyses
to investigate the role of NPs’ mechanical rigidity in the
cellular endocytic process. Experiments based on two types of engineered
Au NPs that have similar properties but different rigidities are performed
in order to investigate their cellular uptake efficiencies, and it
has been found that the more rigid NPs can achieve a higher cellular
uptake efficiency. Simulation results confirm that rigid NPs can achieve
full internalization by forming a complete double-layer endosome coating,
while relatively soft NPs can only reach 40% surface coverage by membrane
lipids. Simulation results capture an intriguing translocation of
multiple NPs with different rigidities in a cooperative manner where
the NPs’ mechanical rigidities regulate their translocation
efficiencies. We find that theoretically rigid NPs require less energy
to overcome the energy barrier for membrane internalization than soft
NPs do, which is in good agreement with experiment and simulation
results. This synergetic study offers useful insight into the design
principle of a general NP-based drug delivery vector as well as the
promising biomedical application of NP-based medicine.