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Modeling receptor‐mediated uptake of polymer‐functionalized iron oxide nanoparticles by macrophages
Author(s) -
Lunov Oleg,
Zablotskii Vitalii,
Syrovets Tatiana,
Roecker Carlheinz,
Tron Kyrylo,
Nienhaus G. Ulrich,
Simmet Thomas
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.773.4
Subject(s) - endocytosis , biophysics , receptor mediated endocytosis , pinocytosis , internalization , clathrin , nanoparticle , chemistry , scavenger receptor , iron oxide nanoparticles , confocal microscopy , membrane , extracellular , superparamagnetism , in vitro , cell membrane , nanotechnology , receptor , microbiology and biotechnology , materials science , biochemistry , biology , physics , lipoprotein , magnetization , quantum mechanics , cholesterol , magnetic field
Although nanosized materials are quickly taken up by macrophages, our understanding of the involved processes is still rather limited. Here we have analyzed the uptake of carboxydextran‐coated superparamagnetic iron oxide particles by human macrophages. In vitro knock‐down and pharmacological approaches revealed that the main uptake mechanism proceeds via clathrin‐dependent, scavenger receptor‐mediated endocytosis. We created a mathematical model of the uptake process that permits determination of key parameters of endocytosis, such as the uptake rate, the mean uptake time, the number of particles per cell, and the correlation between the number of internalized particles and the extracellular concentration. The calculated parameters correlate well with experimental data obtained by spinning disc confocal microscopy. The model also provides information on the individual and collective wrapping time of the nanoparticles and describes the relation between biophysical parameters such as cytoskeletal forces, membrane elasticity and the uptake time. Finally, we also gained information on the minimal linear spacing between simultaneously acting neighboring endocytotic pits that governs the collective uptake process. This model provides novel insight into the biophysical processes involved in endocytosis of nanoparticles. Supported by the DFG, SPP1313.