Membrane Wrapping Efficiency of Elastic Nanoparticles During Endocytosis: Size and Shape Matter

Zhiqiang Shen, Huilin Ye, Xin Yi, and Ying Li

Using coarse-grained molecular dynamics simulations, we systematically investigate the receptor-mediated endocytosis of elastic nanoparticles (NPs) with different sizes, ranging from 25 nm to 100 nm, and shapes, including sphere-like, oblate-like and prolate-like. Simulation results provide clear evidence that the membrane wrapping efficiency of NPs during endocytosis is a result of competition between receptor diffusion kinetics and thermodynamic driving force. The receptor diffusion kinetics refer to the kinetics of receptor recruitment that are affected by the contact edge length between the NP and membrane. The thermodynamic driving force represents the amount of required free energy to drive NPs into a cell. Under volume constraint of elastic NP, the soft spherical NPs are found to have similar contact edge lengths as rigid ones and to less efficiently be fully wrapped due to their elastic deformation. Moreover, the difference in wrapping efficiency between soft and rigid spherical NPs increases with their sizes, due to the increment of their elastic energy change. Furthermore, because of its prominent large contact edge length, the oblate ellipsoid is found to be the least sensitive geometry to the variation in NP's elasticity among the spherical, prolate and oblate shapes during the membrane wrapping. In addition, simulation results indicate that conflicting experimental observations on the efficiency of cellular uptake of elastic NPs could be caused by their different mechanical properties. Our simulations provide a detailed mechanistic understanding about the influence of NPs' size, shape and elasticity on their membrane wrapping efficiency, which serves as a rational guidance for the design of NP-based drug carriers.