Physical Principles of Nanoparticle Cellular Endocytosis - PubMed (original) (raw)

Review

Physical Principles of Nanoparticle Cellular Endocytosis

Sulin Zhang et al. ACS Nano. 2015.

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.

Keywords: cellular uptake; coarse-grained model; endocytosis; ligand−receptor binding; membrane bending; membrane tension; nanomedicine; nanoparticles.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest:

The authors declare no competing financial interest.

Figures

Figure 1

Figure 1

Possible internalization pathways of NPs.

Figure 2

Figure 2

Membrane deformation energies when wrapping a NP.

Figure 3

Figure 3

(a) Schematic illustration of membrane wrapping of a single NP, driven by ligand–receptor binding. Wrapping depletes the receptors in the near vicinity of the NP, creating a receptor concentration gradient that drives the diffusion of the receptors from the remote region to the binding sites. (b) Interrelated effect of NP size and ligand density on the endocytic time of a NP. Reproduced from ref . Copyright 2010 American Physical Society.

Figure 4

Figure 4

Simultaneous entry of multiple NPs. (a) Schematics. (b) Phase diagram of cellular uptake in the space of particle size and ligand density. Reproduced from ref . Copyright 2010 American Physical Society.

Figure 5

Figure 5

Simulation models of lipids at different length scale. (a) All-atom model of the DMPC lipid molecules; (b and c) CG models, a 10-agent (b) and a 3-agent, (c) CG model; and a one-agent-thick membrane model (d). (e) Triangulated membrane model.,

Figure 6

Figure 6

(a–c) Simulation snapshots of the endocytic process of spherocylindrical NPs with different aspect ratios. For all the cases shown, R = 14 nm. (a) ρ = 1; (b) ρ = 1.5; (c) ρ = 2. Here, τ is a characteristic time scale of the model. Color-coded beads represent different coarse-grained constituents. Green, lipids; blue, receptors; yellow, ambient NP surface; red, ligands. (d). Shape effects on the endocytic time of NPs. Evolution of the areal wrapping fraction of NPs with the same radius (R = 10.0_σ_) but different aspect ratios. In the simulations, the spherocylindrical NPs are initially docked on the membrane with their long axes perpendicular to the membrane. Reprinted from ref . Copyright 2013 American Chemical Society.

Figure 7

Figure 7

(a) The bending energy profile for internalizing a spherocylindrical NP (ρ = 2) with different wrapping angles explains the laying-down-then-standing-up process. (red: θ = 0°; black: θ = 90°.). (b) Schematics of the laying-down-to-standing-up process. Images reprinted or adapted from ref . Copyright 2013 American Chemical Society.

Figure 8

Figure 8

(a) Two modes of interaction between a cell membrane and a nanotube. Reproduced from ref . Copyright 2014 American Chemical Society. (b) Elastic energy change as a function of the normalized membrane tension σ¯, where σ¯c=2π/5 is the critical point of transition between these two interaction modes.

Figure 9

Figure 9

(a) Schematic of typical wrapping states and (b and c) wrapping phase diagrams with respect to normalized adhesion energy and membrane tension σ¯ at different values of the rigidity ratio _B_L/B, where _B_L is the bending rigidity of the liposome; (b) 2D case; (c) 3D case. Dashed lines, boundaries between no wrapping and partial wrapping states; solid lines, boundaries between partial and full wrapping states. Adapted with permission from ref . Copyright 2011 American Physical Society.

Figure 10

Figure 10

Left: Cellular uptake of the fluorescent NPs by the cells on polyacrylamide substrates of varying stiffness. Cells were cultured on substrates for 12 h before loading the NPs. Images were taken after loading the NPs for 6 h. Right: The total fluorescence yield of individual cells on the polyacrylamide substrates of varying stiffness obtained by multiplying fluorescence per unit area by the projected cell area on a cell by cell basis. The difference between any two groups at any specified time point of measurement is statistically significant (p < 0.01 using Student t test). Reproduced from ref . Copyright 2013 American Chemical Society.

Figure 11

Figure 11

Left: Representative fluorescence images of SaOS-2 cells on various substrates with distinct surface topographies. Right: Cellular uptake of fluorescent NPs by cells on substrates of different surface topographies. The fluorescence intensities are normalized by the intensity on flat PMMA surface. **Significance at p < 0.01 between any two groups. Reproduced with permission from ref . Copyright 2015 Wiley & Sons, Inc.

Similar articles

Cited by

References

    1. Liu X, Dai Q, Austin L, Coutts J, Knowles G, Zou J, Chen H, Huo Q. A One-Step Homogeneous Immunoassay for Cancer Biomarker Detection Using Gold Nanoparticle Probes Coupled with Dynamic Light Scattering. J Am Chem Soc. 2008;130:2780–2782. - PubMed
    1. Mani V, Chikkaveeraiah BV, Patel V, Gutkind JS, Rusling JF. Ultrasensitive Immunosensor for Cancer Biomarker Proteins Using Gold Nanoparticle Film Electrodes and Multienzyme-Particle Amplification. ACS Nano. 2009;3:585–594. - PMC - PubMed
    1. Stoeva SI, Lee JS, Smith JE, Rosen ST, Mirkin CA. Multiplexed Detection of Protein Cancer Markers with Biobarcoded Nanoparticle Probes. J Am Chem Soc. 2006;128:8378–8379. - PubMed
    1. Qian X, Peng X-H, Ansari DO, Yin-Goen Q, Chen GZ, Shin DM, Yang L, Young AN, Wang MD, Nie S. In Vivo Tumor Targeting and Spectroscopic Detection with Surface-Enhanced Raman Nanoparticle Tags. Nat Biotechnol. 2008;26:83–90. - PubMed
    1. Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology Applications in Cancer. Annu Rev Biomed Eng. 2007;9:257–288. - PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources