Computer Simulations On The Nanoscale Rotational Behaviors Of Nanoparticles On The Cell Membranes

Protein-involved cellular processes occur on/in the cell membrane, are necessary for normal cellular activities. The nanoscale motions of these proteins, such as the sophisticated configuration changes under the lipids’ interactions, are critically important for their biological functions. However, it is still a huge challenge to understand the mechanism of these nanoscale motions. Herein we use the nanoparticle as the model of a protein to explore these motions, especially rotations, on the cell membrane. Furthermore, more and more evidences demonstrate that regulation of nanoparticles’ movements on the membrane is one key for some biomedical applications such as the design of nanoparticle-based diagnostic and therapeutic agents to cells.By means of dissipative particle dynamics simulations, we report a simple but effective way to control rotational behaviors of a nanoparticle, especially spin, on the cell membrane by asymmetrical modification of the particle surface with ligands. It is found by the simulations that the rotation of nanoparticle is strongly influenced by these ligands. When the ligands coating on the two half-surfaces of the nanoparticle are totally same, the membrane could internalize the particle, and a surprising out-of-plane rotation of nanoparticle appears. Such a rotation, from“laying-down” to “standing-up”, is the result of the breaking of the symmetry of curvature energy landscape caused by the anisotropic particle shape. However, if the ligands on two half-surfaces of the nanoparticle are different, only membrane binding is observed in the simulations. Interestingly, it is observed that, with the change of the chain length or rigidity of the ligands, the nanoparticle could spontaneously spin and prefer to bind to the membrane with the half-surface coated by the shorter or more rigid ligands, no matter what the initial orientation of the nanoparticle is. Such a spontaneous rotational behavior of the nanoparticle on a membrane surface and the correspondingly preferred interaction configurations between them are tightly associated with the conformation transitions of ligands and the deformations of the membranes. These findings will be very helpful to develop novel imaging agents for cell membranes with super resolution, as well as provide accurate binding points for drugs and gene. Moreover, it will also help us understand how to precisely control the nanoscale motions of NPs and proteins on the cell membrane.