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

Orr, Galya and Panther, David J. and Cassens, Kaylyn J. and Phillips, Jaclyn L. and Tarasevich, Barbara J. and Pounds, Joel G. (2009) Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane. Toxicology and Applied Pharmacology, 236 (2). 210 - 220.

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Official URL: http://www.sciencedirect.com/science/article/B6WXH...

Abstract

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 can increase particle internalization, and in some cases can 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 in a wide range of industrial applications, and are 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 sulfate proteoglycans play a critical role in 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 sulfate proteoglycan, syndecan-1, is found to mediate the initial interactions of the particles at the cell surface, 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 internalization 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.

Item Type:Article
Uncontrolled Keywords:Toxicity; Biocompatibility; Proteoglycan; Syndecan; Silica; Alveolar; Actin; Macropinocytosis
Subjects:NanoSafety > Environment, health and safety aspects of nanotechnology
ID Code:5683
Deposited By:SPI
Deposited On:28 Jul 2009 15:27
Last Modified:28 Jul 2009 15:27

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