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Quantum dots modulate intracellular Ca2+ level in lung epithelial cells
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellulär biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellulär biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellulär biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab. AstraZeneca R&D, Sweden.
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellulär biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
Vise andre og tillknytning
2017 (engelsk)Inngår i: International Journal of Nanomedicine, ISSN 1176-9114, E-ISSN 1178-2013, Vol. 12, s. 2781-2792Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
DOVE MEDICAL PRESS LTD , 2017. Vol. 12, s. 2781-2792
Emneord [en]
Calu-3 epithelial layer, quantum dot, intracellular Ca2+ concentration [Ca2+](i), transepithelial electrical resistance, cell movement
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-206308DOI: 10.2147/IJN.S130136ISI: 000398663200001Scopus ID: 2-s2.0-85017256402OAI: oai:DiVA.org:kth-206308DiVA, id: diva2:1093367
Merknad

QC 20170505

Tilgjengelig fra: 2017-05-05 Laget: 2017-05-05 Sist oppdatert: 2019-10-20bibliografisk kontrollert
Inngår i avhandling
1. Fluorescent quantum dots and graphene-based sensors for forensic applications
Åpne denne publikasjonen i ny fane eller vindu >>Fluorescent quantum dots and graphene-based sensors for forensic applications
2019 (engelsk)Licentiatavhandling, med artikler (Annet vitenskapelig)
Abstract [en]

A key emerging concept within the forensic sciences today areportable measurementdevices, where a much more efficient usage of the resources involved with crime-solving is possible if confirmatory measurements can be realised directly at a crimescene with such devices. Today, the majority of the presently used methods duringcriminal investigation at a crime scene involves measurements of a presumptivenature, which is a vital tool as it enables the screening of samples. In this thesis,the overarching goal is the development of tool kits for the analysis of biosampleson-site at a crime scene. This is mainly investigated through two routes: theusage of Quantum Dots (QDs) as a recognition element in sensory applications andfabrication of a graphene-based device for the detection of illicit drugs.The investigations conducted for the studies presented in this thesis focuses onsensory applications with a forensic detection scheme in mind: study I reveals in-trinsic properties of QDs to better understand sensing mechanisms upon bindinginteractions; study II demonstrates the fabrication of a graphene-based device forthe detection of illicit drugs; study III showcases the functionalised and bioconju-gated of QDs for a specific investigation into a biological process; study IV furtherthe investigation into the possible side-effects of QDs on biological specimens.In study I we numerically and experimentally investigate the intrinsic blinkingcharacteristics of CdSe-CdS/ZnS QDs. This includes a thorough examination of theexperimental parameters of the measurement setup: the bin time and excitationpower. Different mechanisms between the off- and on-state probability distributionsare found, wherein the on-state follows the random telegraph signal theory and theoff-state follows the inverse power law distribution.In study II, the detection of illicit drugs (amphetamine and cocaine) is achievedthrough graphene-based sensors processed to contain metal electrodes with superioradhesion and low contact resistance. The construction of a microfluidic system isfurther realised for a detection of molecules based on non-covalent interactions.With this system, a wavelength-dependent photoactivity for amphetamine and arange of its chemical analogs is demonstrated. A molecule dependent interactionwith the graphene surface is shown of the graphene surface either in the form ofp-doping (cocaine) or n-doping (amphetamine).Study III investigates the endocytic pathway of the vascular cell adhesionmolecule 1 (VCAM1) in Human Umbilical Vein Endothelial Cells (HUVECs) in-iiiivABSTRACTduced by Tumor Necrosis Factorα(TNFα) with the usage of 3-Mercaptopropionicacid coated (3MPA)-QDs and 5-Carboxyfluorescein (5FAM) functionalised and la-belled with VCAM1 binding peptides, respectively. Internalisation of the VCAM1molecules into lysosomes is shown with light microscopy through observations ofdifferent pathways of the 5FAM labelled peptides and functionalised QDs.In study IV we investigate the adverse effects of 3MPA-QDs on the humanairway epithelium by an examination of the calcium response in lung cells upon astimulation with QDs. The cellular response to the deposition of QDs is observedwith light microscopy and electrical measurements as a global increase of Ca2+in the epithelial layers and a transient decrease in the electrical response. Theseobservations imply that the influx of calcium caused by the QD deposition is inducedby mechanical stressIn an additional ongoing study, the age determination of dried blood spotsare investigated with the usage of protein markers commonly found in the blood.Human serum (HS) is spiked with a marker of interest to mimic those of normallevels in adult human males. After which the HS is allowed to undergo an ageingprocess in a 96 well plate and further analysed in terms of the enzymatic activitywith commercially available kits. The preliminary test results show that there is ameasurable change of activity dependenton the utilised marker that may act as abasis for the age determination of dried blod spots

sted, utgiver, år, opplag, sider
KTH Royal Institute of Technology, 2019. s. 119
Serie
TRITA-SCI-FOU ; 2019:42
Emneord
Graphene, Quantum Dots, Blood, Forensics, Drugs
HSV kategori
Forskningsprogram
Biologisk fysik
Identifikatorer
urn:nbn:se:kth:diva-262750 (URN)978-91-7873-307-1 (ISBN)
Presentation
2019-10-18, Pascal, Tomtebodavägen 23a, Solna, 10:00 (engelsk)
Opponent
Veileder
Forskningsfinansiär
Swedish Foundation for Strategic Research , Forskningsinstitutsdoktorand 2015
Merknad

Examinator: Professor Björn Önfelt

Tilgjengelig fra: 2019-10-21 Laget: 2019-10-20 Sist oppdatert: 2019-10-21bibliografisk kontrollert

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