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Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles

Cedervall, Tommy; Lynch, Iseult; Lindman, Stina; Berggård, Tord LU ; Thulin, Eva; Nilsson, Hanna; Dawson, Kenneth A. and Linse, Sara (2007) In Proceedings of the National Academy of Sciences 104(7). p.2050-2055
Abstract
Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with,... (More)
Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
104
issue
7
pages
2050 - 2055
publisher
National Acad Sciences
external identifiers
  • wos:000244438500006
  • scopus:33847789142
ISSN
1091-6490
DOI
10.1073/pnas.0608582104
language
English
LU publication?
yes
id
f8c4a918-0306-40b2-8d8f-2cc1fa90c7ee (old id 672947)
date added to LUP
2007-12-11 10:44:28
date last changed
2017-11-12 03:19:36
@article{f8c4a918-0306-40b2-8d8f-2cc1fa90c7ee,
  abstract     = {Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.},
  author       = {Cedervall, Tommy and Lynch, Iseult and Lindman, Stina and Berggård, Tord and Thulin, Eva and Nilsson, Hanna and Dawson, Kenneth A. and Linse, Sara},
  issn         = {1091-6490},
  language     = {eng},
  number       = {7},
  pages        = {2050--2055},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles},
  url          = {http://dx.doi.org/10.1073/pnas.0608582104},
  volume       = {104},
  year         = {2007},
}