International Journal of Biological Macromolecules
Interaction of silica nanoparticles with tau proteins and PC12 cells: Colloidal stability, thermodynamic, docking, and cellular studies
Introduction
Nanomaterials are potentially helpful particles in the biomedicine and biotechnology as they are of comparable size to main biological components such as DNA and proteins. This almost identical size can increase the probability of interaction between nanomaterials and biological systems [1,2]. Recently, a number of considerable applications of NPs have been reported in the drug delivery systems, nanobiotechnology, biomedical imaging, and enzyme immobilization [[3], [4], [5], [6], [7]]. Therefore, the interaction of NPs with biological systems is unavoidable and the interaction mechanism between NPs, cells and proteins has emerged as a key area of research [[8], [9], [10]]. Most nanomaterials, after interaction with biological systems, are coated by proteins causing to the formation of a protein corona that mainly specify the biological identity of the NPs [11,12]. This protein NP interaction may change the protein structure, expose new residues on the protein surface and disturb the normal protein function [13]. Adsorption of proteins onto the NP surfaces has been shown to induce protein conformational changes, aggregation, and corresponding deactivation [14,15]. The urgency to reveal the toxicological effect and the design of early indicators to detect potential adverse health effects deriving from the application of nanomaterials is most obvious and some well-known toxicity assays should be carried out prior to release to the public. The comparison of cytotoxic effects from various NPs has indicated diverse responses [16].
Because, the adsorbed proteins onto the NP surface control the route of internalization into the cell, distribution, and delivery to the targeted tissues, therefore the interaction of NPs with protein and cell play a considerable role in the designing and development of NPs for therapeutic applications. Currently, the mechanism of protein absorption and interaction of cells onto/with the NPs is not well characterized.
SiO2 NPs have been applied for various biomedical applications. For example, mesoporous SiO2-coated iron oxide NPs have been used for predictable heating and positive MRI contrast agent [17]. Also, effective delivery of immunosuppressive drug molecules has been done by SiO2coated iron oxide NPs [18]. In the other study, tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous SiO2 NPs-based drug delivery system has been carried out [19]. They have also been used for controlled release and intracellular protein delivery systems [20].
Upon administration and inhalation of SiO2 NPs, they can enter into the nervous system and interact with common human brain proteins and neurons [21].
Tau presents largely in the axons of the central nervous system (CNS) and is known as microtubule associated proteins (MAPs). Tau shows a natively unfolded structure with three different domains of amino-terminal, carboxyl-terminal, and repeat domains and represents a hydrophilic conformation [22,23]. In fact, data from a number of biophysical methods like Raman spectroscopy and nuclear magnetic resonance (NMR) demonstrate that the tau molecule is intrinsically unfolded [24,25]. This means that the polypeptide chain has only a low content of secondary structures such as α-helix and β-sheets, and high content of random coil structure. Tau could establish transient interactions with a various proteins and ions, and maybe NPs in the crowded environment of a cell. In spite of the unfolded structure, tau may shows a folded and aggregated structure upon interactions with ligands, where the amino-terminal, carboxyl-terminal, and repeat domains approach each other.
Because, neurons do not divide, they are not usually used for the cytotoxic studies of NPs on the CNS in vitro. Therefore, neuronal-like cells with a high proliferative capacity are commonly utilized for cellular and molecular studies to monitor the NP-related CNS cytotoxicity. Up-to-date, a sparse number of in vitro studies have been reported using neural-like cell lines for testing the cytotoxicity effect of SiO2 NPs. Some reports have demonstrated cytotoxicity effect of copper oxide NPs, silver NPs, iron NPs, graphene NPs, single-wall carbon nanotubes and multi-wall carbon nanotubes against PC12 cells (a rat cell line with a neuronal-like phenotype) [1,[26], [27], [28], [29]].
Here, we analyzed the colloidal stability of SiO2 NPs in the absence and presence of tau by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Also, the effect of different concentrations of SiO2 NPs on the intrinsic fluorescence intensity of tau was investigated to calculate the thermodynamic parameters. Molecular docking study was also carried out to explore more detailed data regarding the SiO2 NPs interaction with tau at the binding site. Also, the growth characteristics of PC12 cells as neuronal-like cells line in the presence of SiO2 NPs were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT), acridine orange/ethidium bromide (AO/EB) dual staining and flow cytometry assays.
Section snippets
Materials
SiO2 NPs (15–20 nm, spherical, nonporous and amorphous was purchased from US Research Nanomaterials, Inc., US3436). The cell culture medium (DMEM), penicillin–streptomycin, fetal bovine serum (FBS) were obtained from Gibco BRL (Life technology, Paisley, Scotland). AB, AO, MTT, and dimethyl sulfoxide (DMSO) were purchased from Merck Co. (Darmstadt, Germany). PC12 cell line (rat adrenal pheochromocytoma cells) was obtained from Pasture institute of Tehran, Tehran Iran. All other chemicals were of
TEM and DLS measurements
TEM observation was carried out to monitor the diameter distribution and morphology of SiO2 NPs in the absence and presence of tau. Fig. 1(a) exhibited that SiO2 NPs have a diameter of around 20 nm with a semi rounded shape. However, after addition of tau protein to the SiO2 NPs sample, the proteins are adsorbed onto the NP surface and result in the agglomeration of NPs [Fig. 1(b)].
To explore the size and distribution of SiO2 NP in the solution, DLS technique was also carried out. As shown in
Conclusion
The behavior of SiO2 NPs in the nervous system was evaluated by biophysical, docking and cellular studies. The colloidal stability of the SiO2 NPs in the presence of tau was reduced. SiO2 NPs formed a static complex with tau and bound to the tau with high affinity by means of hydrogen bonds and van der Waals interactions. Ser, Thr and Tyr residues established hydrogen bonds with the surface of SiO2 NPs. Cellular assays reveled that SiO2 NPs can trigger cytotoxicity through apoptosis and
Acknowledgment
The financial support of Islamic Azad University, Pharmaceutical Science branch (IAUPS) is greatly acknowledged. Tau protein was gifted by Dr. Koorosh Shahpasand from Royan Institute for Stem Cell Biology and Technology, Tehran, Iran.
Conflict of interest
The author declare no conflict of interest.
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These authors contributed equally to this work.