Shape-dependent internalization kinetics of nanoparticles by membranes

Internalization of nanoparticles by biomembranes is critical for nanomedicine development; however, this process, especially its dynamics aspect, is still not well understood. Using coarse-grained molecular modeling combined with free energy calculations, we studied the endocytic process for spherical, prolate and oblate particles with varied aspect ratios, volumes and interaction strengths. Rich dynamic wrapping behaviors have been observed. Small ellipsoids follow a pathway that includes particle laying-down, membrane invagination and wrapping, and then disruption of the membrane neck. However, the step of particle laying-down is skipped for large ellipsoids. Because of the significantly decreased local mean curvature at the side edge (oblate ellipsoid) or tips (prolate ellipsoid), the rotation is less favorable for particles with larger volume. Given the existence of a local minimum and an energy barrier during the endocytic process presented by our free energy calculations, the oblate particle provides longer endocytic time than the corresponding prolate particle. For large particles, the free energy surfaces are smooth, with no local minimum. When we increase the interaction strength between the membrane and the particle, the endocytic process is greatly affected. Moreover, a "sandwiched structure", in which the particle lays between the two membrane layers, was observed for both prolate and oblate particles. Coarse-grained molecular modeling combined with free energy calculations was employed to study the effects of shape anisotropy on particle internalization and the mechanism of the endocytic process, especially the dynamics aspect of particle internalization.