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Nanoparticles’ unexpected disruptions to endothelial and epithelial functions.

DtL Speaker: David Tai Leong
Assistant Professor,
Chemical and Biomolecular Engineering, National University of Singapore, Singapore


Date: June 18, 2015
Time: 12:30-1:30 pm
Place: 665 Huntington Ave,
Bldg. 1, Room 1302,
Boston, MA, 02115

Abstract: The endothelium and epithelium are important classes of cells that control passages of molecules through important interfaces within the body. The endothelium while is not the usual target tissue of action, is almost certainly a tissue that most nanomaterials (nanosafety concerns or nanomedicine) would interact with. This interaction with the endothelium is therefore an important factor to consider. We have shown that inorganic nanomaterials (TiO2, SiO2 and silver) caused endothelial leakiness (both in vitro and in vivo). The mechanism was that these nanomaterials enter and bind to VE-cadherin found in the adherens junctions between endothelial cells and disrupted the critical junction holding the cells together, leading to intracellular signaling that led to a leakiness phenotype and we coined this as Nanoparticle induced endothelial leakiness (NanoEL). The overall impact of NanoEL to nanotechnology is that it might be the real nanoparticle induced effect hidden under the guise of the tumor derived EPR effect. The epithelium heals wound through an orchestrated and coordinated migration of cells along the plane of the substrate to seal up any gaps. Due to the urgency of reforming an integral protective layer, epithelial cells have one of the fastest migration speeds amongst all cell types. Using a wound healing and cell traction force assays, we have shown that TiO2, SiO2 and HA nanoparticles hindered epithelial cell migration. This effect is mediated by uptake and subsequently disruption of microtubules that distorted the dynamic force equilibrium within the cell between cell adhesion and intracellular forces. Both of these effects brought into sharper focus on functional impairment effects of nanoparticles on cells.

Biographical Sketch: Dr. Leong graduated with a Bachelor of Chemical Engineering and a PhD in Biology from National University of Singapore (NUS). He did his postdoctoral training in the Howard Hughes Medical Institute, University of Pennsylvania and return to his alma mater as a Lee Kuan Yew Postdoctoral Fellow. He subsequently joined the Department of Chemical and Biomolecular Engineering, NUS as an Assistant Professor in late 2010. His research interests includes finding new nanomaterials effects on cells and figuring out their mechanisms and creating new DNA based nanostructures with new applications.