Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization

Philip J Smith¹, Maude Giroud², Helen L Wiggins², Florence Gower², Jennifer A Thorley², Bjorn Stolpe³, Julie Mazzolini², Rosemary J Dyson⁴, Joshua Z Rappoport^2
1Physical Sciences of Imaging for the Biomedical Sciences (PSIBS) Doctoral Training Center, School of Chemistry, ²School of Biosciences, ³School of Geography, Earth, and Environmental Sciences, ⁴School of Mathematics, University of Birmingham, Edgbaston, Birmingham, United Kingdom

Abstract: Increasing production and application of nanomaterials raises significant questions regarding the potential for cellular entry and toxicity of nanoparticles. It was observed that the presence of serum reduces the cellular association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20-fold, relative to cells incubated in serum-free media. Analysis by confocal microscopy demonstrated that the presence of serum greatly reduces the cell surface association of nanoparticles, as well as the potential for internalization. However, both in the presence and absence of serum, nanoparticle entry depends upon clathrin-mediated endocytosis. Finally, experiments performed with cells cooled to 4°C suggest that a proportion of the accumulation of nanoparticles in cells was likely due to direct permeabilization of the plasma membrane.

Keywords: nanoparticles, polystyrene beads, serum, endocytosis, dynamin, clathrin, permeabilization

Corrigendum for this paper has been published