Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane

The cellular interactions and pathways of engineered submicro- and nano-scale particles dictate the cellular response and ultimately determine the level of toxicity or biocompatibility of the particles. Positive surface charge call increase particle internalization, and in some cases call also increase particle toxicity, but the underlying Mechanisms are largely unknown. Here we identify the cellular interaction and pathway of positively charged submicrometer synthetic amorphous silica Particles, which are used extensively ill a wide range of industrial applications, and lie explored for drug delivery and medical imaging and sensing. Using time lapse fluorescence imaging in living cells and other quantitative imaging, approaches, it IS found that heparan surface proteoglycans play a critical role ill the attachment and internalization of the particles in alveolar type II epithelial cell line (C10), a potential target cell type bearing apical microvilli. Specifically. the transmembrane heparan surface proteoglycan, syndecan-1, is found to mediate the initial interactions of the particles at the cell Sulfate, their coupling With actin filaments across the cell membrane, and their subsequent internalization via macropinocytosis. The observed interaction of syndecan molecules With the particle prior to their engagement with actin filaments suggests that the particles initiate their own by facilitating the clustering of the molecules, which is required for the actin coupling and subsequent internalization of syndecan. Our observations identify a new role for syndecan-1 in mediating the cellular interactions and fate of positively charged submicrometer amorphous silica particles in the alveolar type II epithelial cell, a target cell for inhaled particles. (C) 2009 Elsevier Inc. All rights reserved.