Microvilli Adhesion: An Alternative Route for Nanoparticle Cell Internalization

Abstract

The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated. This microvillus-mediated adhesion (MMA) has been observed using ceria and magnetite NPs with a dimension of <40 nm functionalized with polyacrylic acid but not using NPs with a neutral or positive functionalization. Such an adhesion was not cell specific, as it was demonstrated in three different cell lines. MMA was also reduced by modifications of the microvillus lipid rafts, obtained by depleting cholesterol and altering synthesis of sphingolipids. We found a direct relationship between MAA, cell cycle, and density of microvilli. The evidence suggests that MMA differs from the commonly described uptake mechanisms and might represent an interesting alternative approach for selective NP delivery.

Fluorescent Artificial Antigens Revealed Extended Membrane Networks Utilized by Live Dendritic Cells for Antigen Uptake

“…We first synthesized water-soluble QDs coated with 40% octylamine-modified polyacrylic acid, which has been recently reported to facilitate microvillus-mediated adhesion and cell internalization . The hydrodynamic diameter of the QD was determined to be 87 nm in our previous work .…”

“…A recent report suggested that polyacrylic acid coating facilitated microvilli adhesion and internalization of nanoparticles. 26 Our FAAs possibly first attached to the exterior of the plasma membrane of DCs, followed by internalization and intracellular migration (Figure 2a). From the asymmetrical shape of the image and intensity trajectories of FAAs, we determined that most FAAs consisted of clusters of QDs (Figures 2b and S6).…”

“…adhesion and cell internalization. 26 The hydrodynamic diameter of the QD was determined to be 87 nm in our previous work. 27 The polyacrylic-acid-coated QDs were subsequently termed fluorescent artificial antigens (FAAs).…”

“…Here, we introduce an effective labeling method using fluorescent artificial antigens (FAAs). The FAAs are based on semiconductor quantum dots (QDs) coated with octylamine-modified polyacrylic acid, which has been reported to facilitate microvillus-mediated adhesion and cell internalization . Using single-particle tracking of FAAs, we discovered extended membrane networks from live DC2.4 mouse dendritic cells and characterized their morphology with superresolution.…”

Early enteric and hepatic responses to ingestion of polystyrene nanospheres from water in C57BL/6 mice

“…The 50 nm diameter of clathrin-coated pits on the hepatocyte plasma membrane may explain appearance of 20 nm but not 200 nm PSNS in putative endosomes. A recent report in cell culture (Sommi et al, 2021) demonstrates a role for microvillus-mediated adhesion as an alternative route for internalization of nanoparticles with an upper diameter limit of 70-80 nm. Further, a polyanionic surface is necessary for this interaction.…”