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Virus-inspired design principles of nanoparticle-based bioagents.

Yuan H, Huang C, Zhang S - PLoS ONE (2010)

Bottom Line: The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics. Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation. Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect. Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25-30 nm, and optimally several tens of ligands should be coated onto NPs. These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.

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Membrane tension and the bulk density of NPs regulate the upper bound of the uptake rate, but hardly affect the lower bound.
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pone-0013495-g009: Membrane tension and the bulk density of NPs regulate the upper bound of the uptake rate, but hardly affect the lower bound.

Mentions: The bulk density of NPs in solution appeared as a model parameter only for computing the cellular uptake. A high bulk density yields a high surface concentration of NPs on cell membrane, leading to intensified competition for receptors among adhering NPs [20], [31] and high entropic penalty for concentrating receptors onto NP surfaces. This follows that increasing the bulk density of NPs decreases the adhesion strength, and therefore shifts the upper bound of the uptake rate downward. Since the bulk density only affects the entropy of the receptors, the lower bound of uptake rate is hardly affected, as shown in Fig. 9. Cells may actively modulate their membrane tension under different physiological conditions through various mechanisms such as membrane reservoir release, lipid molecules insertion into cell membrane, interference from the cortical actin network [37], etc. A high membrane tension corresponds to a high deformation energy cost, and hence increases the endocytic time and reduces the cellular uptake and uptake rate. We have pointed out that the relative significance of the membrane tension and bending defines a characteristic particle radius beyond (below) which membrane tension (bending) dominates the physics. Thus, the effect of membrane tension is negligible for small particles but significant for large particles. This follows that membrane tension primarily regulates the upper bound of the uptake rate, but hardly affects the lower bound, as shown in Fig. 9.


Virus-inspired design principles of nanoparticle-based bioagents.

Yuan H, Huang C, Zhang S - PLoS ONE (2010)

Membrane tension and the bulk density of NPs regulate the upper bound of the uptake rate, but hardly affect the lower bound.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957438&req=5

pone-0013495-g009: Membrane tension and the bulk density of NPs regulate the upper bound of the uptake rate, but hardly affect the lower bound.
Mentions: The bulk density of NPs in solution appeared as a model parameter only for computing the cellular uptake. A high bulk density yields a high surface concentration of NPs on cell membrane, leading to intensified competition for receptors among adhering NPs [20], [31] and high entropic penalty for concentrating receptors onto NP surfaces. This follows that increasing the bulk density of NPs decreases the adhesion strength, and therefore shifts the upper bound of the uptake rate downward. Since the bulk density only affects the entropy of the receptors, the lower bound of uptake rate is hardly affected, as shown in Fig. 9. Cells may actively modulate their membrane tension under different physiological conditions through various mechanisms such as membrane reservoir release, lipid molecules insertion into cell membrane, interference from the cortical actin network [37], etc. A high membrane tension corresponds to a high deformation energy cost, and hence increases the endocytic time and reduces the cellular uptake and uptake rate. We have pointed out that the relative significance of the membrane tension and bending defines a characteristic particle radius beyond (below) which membrane tension (bending) dominates the physics. Thus, the effect of membrane tension is negligible for small particles but significant for large particles. This follows that membrane tension primarily regulates the upper bound of the uptake rate, but hardly affects the lower bound, as shown in Fig. 9.

Bottom Line: The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics. Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation. Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect. Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25-30 nm, and optimally several tens of ligands should be coated onto NPs. These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.

Show MeSH
Related in: MedlinePlus