Role of Different Dimensions of Skeleton Proteins in the Endocytosis of Various Shaped Nanoparticles

Nanoparticles (NPs) have been widely used in biomedical applications such as gene/drug delivery carriers, molecular imaging, and diagnostics. Among the physicochemical properties, shape and size are vital design parameters for tuning the cell uptake of NPs. However, the regulatory mechanism remains elusive due to the complexity of the cell membrane and the role of cytoskeletons. Therefore, in this work, a computational simulation technique is applied to investigate the influence of different dimensional skeleton proteins on the endocytosis of different-shaped NPs (sphere, rod, and disk). Our simulation results show that different dimensions of cytoskeletons can mediate selective endocytosis for different sizes and shapes of NPs. It was found that one-dimensional skeleton proteins could not help small NPs overcome membrane bending and endocytosis. We found a very interesting phenomenon. When the one-dimensional cytoskeleton limits the sinking of shape anisotropic NPs from one dimension, the NPs can respond intelligently by rotating themselves and adjusting their way to endocytosis. Two-dimensional skeleton proteins inhibited the endocytosis of NPs by restricting plasma membrane flow in both directions, while three-dimensional skeleton proteins significantly promoted the endocytosis of small NPs with different shapes. Understanding the role of different dimensions of skeleton proteins in NP endocytosis will be helpful for the design of highly efficient nanomaterials as drug/gene delivery carriers.