Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Li, Long; Zhang, Yudie; Wang, Jizeng

doi:10.1098/rsos.170063

Cited by 24 publications

(14 citation statements)

References 55 publications

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“…[44][45][46] Furthermore, depending on the origin of the cells, cell surface receptor density is different, which might impact NP-cell association and ultimately NP uptake. 47 The latter supports the similar NP-cell association for A549 and 16HBE14o-, both human lung epithelial cells. Moreover, NPs can be internalized by various endocytic mechanisms (e.g., caveolin-mediated and clathrin-mediated endocytosis).…”

Section: Cell Associated Aunpssupporting

confidence: 68%

Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes

et al. 2020

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Section: Cell Associated Aunpssupporting

confidence: 68%

Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes

et al. 2020

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“…Particle uptake at the cellular level is governed by many factors associated with the highly complex endocytic and intracellular trafficking pathways as reviewed in (26). In addition, the diffusion of the transporter molecule or particle-specific receptor proteins in the plasma membrane can influence particle uptake (36). However, in the absence of cell type-specific quantitative information, incorporation of such details entails more parameters and associated uncertainties in a model.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of the Correlation between Cell Size and Cellular Uptake of Particles

Khetan

Shahinuzzaman

Barua

et al. 2019

Biophysical Journal

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The size of a cell is central to many functions, including cellular communication and exchange of materials with the environment. This modeling and experimental study focused on understanding how the size of a cell determines its ability to uptake nanometer-scale extracellular materials from the environment. Several mechanisms in the cell plasma membrane mediate cellular uptake of nutrients, biomolecules, and particles. These mechanisms involve recognition and internalization of the extracellular molecules via endocytic components, such as clathrin-coated pits, vacuoles, and micropinocytic vesicles. Because the demand for an external resource could be different for cells of different sizes, the collective actions of these various endocytic routes should also vary based on the cell size. Here, using a reaction-diffusion model, we analyze single-cell data to interrogate the one/one mapping between the size of the MDA-MB 231 breast cancer cells and their ability to uptake nanoparticles. Our analysis indicates that under both reaction-and diffusion-controlled regimes, cellular uptake follows a linear relationship with the cell radius. Furthermore, this linear dependency is insensitive to particle size variation within 20-200 nm range. This result is counterintuitive because the general perception is that cellular uptake is proportional to the cell volume (mass) or surface area and hence follow a cubic or square relationship with the cell radius. A further analysis using our model reveals a potential mechanism underlying this linear relationship.

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“…Both theoretical and computational studies suggest that the inhomogeneous distribution of ligands on a NP surface can prohibit the endocytosis of NPs. 48,62 For instance, Schubertová et al explored the influence of the ligand distribution on the cellular uptake efficiency of rigid NPs through coarse-grained molecular simulations. 48 The simulation results reveal that the NPs with homogeneous ligand distributions demonstrate fast membrane wrapping and cellular uptake, while the diffusion of ligands on the NP surface can delay and block the uptake of NPs, due to the ligand-free NP surface.…”

Section: Correlation With Theoretical and Experimental Observationsmentioning

confidence: 99%

Aggregation of polyethylene glycol polymers suppresses receptor-mediated endocytosis of PEGylated liposomes

Shen

Kröger

et al. 2018

Nanoscale

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The PEGylated liposome, composed of an aqueous core and a fluid state lipid bilayer shell, is one of the few Food and Drug Administration (FDA) approved drug delivery platforms. To prevent the absorption of serum proteins, the surface of a liposome is decorated by hydrophilic and bio-compatible polyethylene glycol (PEG) polymers, which can significantly extend the blood circulation time of liposomes. In this work, with the help of dissipative particle dynamics (DPD) simulations, we explore how the tethered PEG polymers will affect the membrane wrapping process of PEGylated liposomes during endocytosis. Specifically, we compare the membrane wrapping process of a PEGylated rigid nanoparticle (NP) with a PEGylated liposome under identical conditions. Due to the mobility of grafted PEG polymers on the liposome's surface, the complete wrapping of a PEGylated liposome can be dramatically delayed and blocked, in comparison with a PEGylated rigid NP. For the first time, we observe the aggregation of PEG polymers in the contact region between a PEGylated liposome and the membrane, which in turn leads to a ligand-free region on the surface of the liposome during endocytosis. Subsequently, the partially wrapped PEGylated liposome can be bounced back to a less wrapped state. Through free energy analysis, we find that the aggregation of PEG polymers during the membrane wrapping process of a PEGylated liposome introduces a dramatic free energy penalty of about ∼800kT, which is almost twice that of a PEGylated rigid NP. Here k and T are the Boltzmann constant and temperature, respectively. Such a large energy barrier and the existence of a ligand-free region on the surface of PEGlylated liposomes prevent their membrane wrapping, thereby reducing the chance of internalization by tumor cells. Therefore, our DPD simulation results provide a possible explanation for the inefficient cellular uptake of PEGylated liposomes. In addition, we suggest that by increasing the repulsive interactions between grafted PEG polymers it might be possible to limit their aggregation, and in turn, facilitate the internalization of PEGylated liposomes. The current study provides fundamental insights into the endocytosis of PEGylated liposomes, which could help to design this platform with high efficacy for drug delivery.

show abstract

Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Cited by 24 publications

References 55 publications

Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes

Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes

Quantitative Analysis of the Correlation between Cell Size and Cellular Uptake of Particles

Aggregation of polyethylene glycol polymers suppresses receptor-mediated endocytosis of PEGylated liposomes

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