Physical Principles of Nanoparticle Cellular Endocytosis

Abstract

This review article focuses on the physiochemical mechanisms underlying nanoparticle uptake into cells. When nanoparticles are in close vicinity to a cell, the interactions between the nanoparticles and the cell membrane generate forces from different origins. This leads to the membrane wrapping of the nanoparticles followed by cellular uptake. This article discusses how the kinetics, energetics, and forces are related to these interactions and dependent on the size, shape, and stiffness of nanoparticles, the biomechanical properties of the cell membrane, as well as the local environment of the cells. The discussed fundamental principles of the physiochemical causes for nanoparticle–cell interaction may guide new studies of nanoparticle endocytosis and lead to better strategies to design nanoparticle-based approaches for biomedical applications.

Nanoparticle–membrane interactions

“…For example, for a cell membrane tension in the order of 0.05 mNÁm ¡1 and bending modulus values of 15 k B T, the length scale is approximately 50 nm [48]. Simulation [59] and experiment [60] suggest a bending modulus of k » 23 k B T (»10 ¡19 J at 300 K for DPPC gives »60 nm.…”

“…These mechanisms are in most cases controlled by the cell membrane via specific receptor-mediated interactions (eg clathrin, caveolin, flotollin mediated endocytosis) [42,44,45]. However, it has been demonstrated that NPs can also traverse the cell membrane via endocytosis (or exocytosis) without being involved in any specific receptor-mediated interaction [46][47][48][49]. Lipid membranes are highly flexible and the bilayer can be deformed due to NP adhesion on its surface leading to a full NP engulfment and its final uptake.…”

“…Assuming a tensionless membrane and that the non-specific adhesion interaction is driving the process, NP engulfment occurs when the adhesion energy is sufficient to overcome the energy cost associated with bending the membrane around the particle surface. For this tensionless case, two parameters, adhesion energy and membrane bending modulus, define a critical radius, r c , representing the minimum particle size for which the NP engulfment occurs [47,48,53,54]:…”

The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations

“…Filament growth and membrane deformation generate forces that promote invagination of the virus 6. Many simulation studies have focused on this process of endocytosis, and provided useful information for understanding this process 7. Cell membranes are considered as the first barrier to defend cells from external harms 8.…”

Liquid Metal Phagocytosis: Intermetallic Wetting Induced Particle Internalization

“…Recently, self‐powered motor,11 jumper,12 oscillator,13 soft actuators,14, 15, 16 and 2D semiconductor skin17 demonstrated with this class of material shed light on their new possibilities toward more diverse applications. Here, we report a particle‐eating phenomenon of gallium‐based LMs, which mimics the biological phagocytosis process (also known as cellular‐eating, a basic cell behavior referring to the transportation of external particles into cells from across the membranes18, 19, 20, 21), and thus we call it LM‐Phagocytosis. Such phenomenon represents a wet‐processing strategy to achieve particle internalization.…”