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

被引:2464
作者
Cedervall, Tommy
Lynch, Iseult
Lindman, Stina
Berggard, Tord
Thulin, Eva
Nilsson, Hanna
Dawson, Kenneth A. [1 ]
Linse, Sara
机构
[1] Univ Coll Dublin, Sch Chem & Chem Biol, Dublin 4, Ireland
[2] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland
[3] Lund Univ, Chem Ctr, Dept Biophys Chem, SE-22100 Lund, Sweden
[4] Lund Univ, Dept Prot Technol, SE-22184 Lund, Sweden
关键词
D O I
10.1073/pnas.0608582104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2050 / 2055
页数:6
相关论文
共 33 条
  • [1] Allemann E, 1997, J BIOMED MATER RES, V37, P229, DOI 10.1002/(SICI)1097-4636(199711)37:2<229::AID-JBM12>3.0.CO
  • [2] 2-9
  • [3] 140 Mouse brain proteins identified by Ca2+-calmodulin affinity chromatography and tandem mass spectrometry
    Berggård, T
    Arrigoni, G
    Olsson, O
    Fex, M
    Linse, S
    James, P
    [J]. JOURNAL OF PROTEOME RESEARCH, 2006, 5 (03) : 669 - 687
  • [4] Synthesis and in vitro characterization of a poly(acrylic acid)-homocysteine conjugate
    Bernkop-Schnürch, A
    Leitner, V
    Moser, V
    [J]. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2004, 30 (01) : 1 - 8
  • [5] COLLOIDAL CARRIERS FOR INTRAVENOUS DRUG TARGETING - PLASMA-PROTEIN ADSORPTION PATTERNS ON SURFACE-MODIFIED LATEX-PARTICLES EVALUATED BY 2-DIMENSIONAL POLYACRYLAMIDE-GEL ELECTROPHORESIS
    BLUNK, T
    HOCHSTRASSER, DF
    SANCHEZ, JC
    MULLER, BW
    MULLER, RH
    [J]. ELECTROPHORESIS, 1993, 14 (12) : 1382 - 1387
  • [6] The potential environmental impact of engineered nanomaterials
    Colvin, VL
    [J]. NATURE BIOTECHNOLOGY, 2003, 21 (10) : 1166 - 1170
  • [7] Plasma protein adsorption patterns on liposomes: Establishment of analytical procedure
    Diederichs, JE
    [J]. ELECTROPHORESIS, 1996, 17 (03) : 607 - 611
  • [8] Influence of surface charge density on protein adsorption on polymeric nanoparticles:: analysis by two-dimensional electrophoresis
    Gessner, A
    Lieske, A
    Paulke, BR
    Müller, RH
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2002, 54 (02) : 165 - 170
  • [9] Nanoparticles with decreasing surface hydrophobicities:: influence on plasma protein adsorption
    Gessner, A
    Waicz, R
    Lieske, A
    Paulke, BR
    Mäder, K
    Müller, RH
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2000, 196 (02) : 245 - 249
  • [10] Functional groups on polystyrene model nanoparticles:: Influence on protein adsorption
    Gessner, A
    Lieske, A
    Paulke, BR
    Müller, RH
    [J]. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2003, 65A (03): : 319 - 326