Mechanics Of Cell Interaction With Intercellular Nanoparticles: Shape-Dependent Competition Between Two-Membrane Trapping And Single-Membrane Wrapping

Understanding the mechanical behaviors of nanoparticles confined between adjacent cells is of fundamental importance to the passage of drug cargoes through cell junctions, where the nanoparticles could have contact with two cell membranes simultaneously. Here we theoretically investigate the adhesive membrane wrapping and trapping of rigid cylindrical and spherical nanoparticles confined by two cell membranes. It is shown that the system energy and configurations depend collectively on the membrane bending rigidity, tension, adhesion energy, and the ratio between the particle size and intermembrane distance. Two fundamental modes of particle-membrane interaction are revealed, two-membrane trapping and single-membrane wrapping. Confined cylindrical nanoparticles remain trapped by two cell membranes and confined spherical nanoparticles could undergo a state transition from two-membrane trapping to single-membrane wrapping as the wrapping degree increases. Corresponding interaction phase diagrams for cylindrical and spherical nanoparticles are established based on the stability of no-wrapping, partial-trapping, partial-wrapping, full-trapping and full-wrapping states. Analytical predictions are also obtained in characterizing the single-membrane wrapping at early wrapping degree. Our results suggest that cylindrical nanoparticles in comparison with spherical nanoparticles might display superior drug penetration in tumors and across epithelial and endothelial barriers, providing guidance in the rational design of anticancer nanomedicine. (C) 2021 Elsevier Ltd. All rights reserved.