| Summary: | Huijuan Yin,1 Jacopo M Fontana,1 Johan Solandt,1,2 Johnny Israelsson Jussi,1 Hao Xu,1 Hjalmar Brismar,1 Ying Fu1 1Section of Cellular Biophysics, Department of Applied Physics, Royal Institute of Technology (KTH), Science for Life Laboratory, Solna, 2AstraZeneca R&D, Mölndal, Sweden Abstract: While adverse effects of nanoparticles on lung health have previously been proposed, few studies have addressed the direct effects of nanoparticle exposure on the airway epithelium. In this work, we examine the response of the pulmonary airway to nanoparticles by measuring intracellular Ca2+ concentration ([Ca2+]i) in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA) coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient transepithelial electrical resistance (TEER) decrease and global [Ca2+]i increase in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and expansion, were observed under QD deposition. This suggests that a QD-induced global [Ca2+]i increase in the Calu-3 epithelial layer caused the transient TEER decrease. The [Ca2+]i increase was marked and rapid in the apical region, while [Ca2+]i decreased in the basolateral region of the epithelial layer. TEER transient response and extracellular Ca2+ entry induced by QD deposition were completely inhibited in cells treated with stretched-activated (SA) inhibitor GdCl3 and store-operated calcium entry (SOCE) inhibitor BTP2 and in cells immersed in Ca2+-free medium. The voltage-gated calcium channel (VGCC) inhibitor nifedipine decreased, stabilized, and suppressed the TEER response, but did not affect the [Ca2+]i increase, due to QD deposition. This demonstrates that the Ca2+ influx activated by QDs’ mechanical stretch occurs through activation of both SA and SOCE channels. QD-induced [Ca2+]i increase occurred in the Calu-3 epithelial layer after culturing for 15 days, while significant TEER drop only occurred after 23 days. This work provides a new perspective from which to study direct interactions between airway epithelium and nanoparticles and may help to reveal the pathologies of pulmonary disease. Keywords: Calu-3 epithelial layer, quantum dot, intracellular Ca2+ concentration [Ca2+]i, transepithelial electrical resistance, cell movement
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