Browsing by Author "Ceylan, H."

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Open Access
Intracellular accumulation of gold nanoparticles leads to inhibition of macropinocytosis to reduce the endoplasmic reticulum stress
(Nature Publishing Group, 2017) Gunduz, Nuray; Ceylan, H.; Güler, Mustafa O.; Tekinay, Ayse B.
Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-Term in vitro cell-death based assays, and analyses of tissue-and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory. Herein, we show intracellular accumulation and the associated toxicity of gold nanoparticles (AuNPs) for over two-months in the cultured vascular endothelial cells. We observed that steady exposure of AuNPs at low (non-lethal) dose leads to rapid intracellular accumulation without causing any detectable cell death while resulting in elevated endoplasmic reticulum (ER) stress. Above a certain intracellular AuNP threshold, inhibition of macropinocytosis mechanism ceases further nanoparticle uptake. Interestingly, the intracellular depletion of nanoparticles is irreversible. Once reaching the maximum achievable intracellular dose, a steady depletion is observed, while no cell death is observed at any stage of this overall process. This depletion is important for reducing the ER stress. To our knowledge, this is the first report suggesting active regulation of nanoparticle uptake by cells and the impact of long-Term exposure to nanoparticles in vitro. © 2017The Author(s).
Open Access
Surface-adhesive and osteogenic self-assembled peptide nanofibers for bioinspired functionalization of titanium surfaces
(Royal Society of Chemistry, 2012) Ceylan, H.; Kocabey, S.; Tekinay, Ayse B.; Güler, Mustafa O.
Mechanical properties and biological inertness of titanium provide potential in orthopedic and dental implants. However, integration of titanium-based implants into the existing tissue is a major problem. Herein, we demonstrate biofunctionalization of titanium surfaces through a mussel-inspired adhesion mechanism conjugated to self-assembled peptide nanofibers in order to overcome biocompatibility issues. A Dopa conjugated peptide nanofiber coating was used along with bioactive peptide sequences for osteogenic activity to enhance osseointegration of medical grade titanium surface, TiAl6V4 alloy. Dopa-mediated immobilization of osteogenic peptide nanofibers on titanium surfaces created an osteoconductive interface between osteoblast-like cells and inhibited adhesion and viability of soft tissue forming fibroblasts compared to the uncoated titanium substrate. This biofunctionalization strategy can be extended into other surface immobilization systems owing to the versatile adhesive properties of Dopa and the ease of ligand conjugation to peptide amphiphile molecules. © 2012 The Royal Society of Chemistry.