Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young’s modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies.
A new approach has been developed to improve sensing performances of electrochemically grown Au nanostructures (AuNSs) based on the pre-seeding of the electrode. The pre-seeding modification is simply carried out by vacuum thermal deposition of 5 nm thin film of Au on the substrate followed by thermal annealing at 500 °C. The electrochemical growth of AuNSs on the pre-seeded substrates leads to impressive electrochemical responses of the electrode owing to the seeding modification. The dependence of the morphology and the electrochemical properties of the AunSs on various deposition potentials and times have been investigated. for the positive potentials, the pre-seeding leads to the growth of porous and hole-possess networks of AunSs on the surface. for the negative potentials, AunSs with carved stone ball shapes are produced. the superior electrode was achieved from AunSs developed at 0.1 V for 900 s with pre-seeding modification. The sensing properties of the superior electrode toward glucose detection show a high sensitivity of 184.9 µA mM −1 cm −2 , with a remarkable detection limit of 0.32 µM and a wide range of linearity. the excellent selectivity and reproducibility of the sensors propose the current approach as a large-scale production route for non-enzymatic glucose detection. During past decades, electrochemical sensing has attracted many attentions due to their considerable advantages such as high sensitivity, low cost, fast response time, wide linear range and portability and widespread applications 1-9. Up to now various types of nanomaterial such as carbon nanotubes 10 , graphene 11,12 , noble metals 13,14 , metal oxides 15 , hybrid 16 and composite nanostructures 17,18 have been developed for electrochemical sensing. Among different nanomaterials, gold nanostructures (AuNSs) have attracted significant interests because of their remarkable electrical and catalytic properties, easy functionalization and excellent biocompatibility. Since the electron transfer and catalytic activity of AuNSs strongly depend on their morphology and their size, extensive researches have been proposed in literatures to develop optimized AuNSs for sensing applications 19,20. The notable approaches between them are based on the electrodeposition 19 , direct electrostatic self-assembly 21 , self-assembly with polymer 22-24 and seed-mediated growth 25-28. In the cases of self-assembly and seed-mediated strategies, the electron transfer and catalytic activity of AuNSs are hindered due to the existence of surfactant and linker molecules surrounding the nanostructures. The electrodeposition is the most reliable approach for shape and size controlled construction of AuNSs due to the possibility of controlling the nucleation and the growth processes. However, in this method the well control of morphology is provided by using template, surfactant or pre-treatment of the substrate that limit the applicability of the method 20,29,30 .
Biomechanical and morphological analysis of the cells is a novel approach for monitoring the environmental features, drugs, and toxic compounds’ effects on cells. Graphene oxide (GO) has a broad range of medical applications such as tissue engineering and drug delivery. However, the effects of GO nanosheets on biological systems have not been completely understood. In this study, we focused on the biophysical characteristics of cells and their changes resulting from the effect of GO nanosheets. The biophysical properties of the cell population were characterized as follows: cell stiffness was calculated by atomic force microscopy, cell motility and invasive properties were characterized in the microfluidic chip in which the cells are able to visualize cell migration at a single-cell level. Intracellular actin was stained to establish a quantitative picture of the intracellular cytoskeleton. In addition, to understand the molecular interaction of GO nanosheets and actin filaments, coarse-grained (CG) molecular dynamics (MD) simulations were carried out. Our results showed that GO nanosheets can reduce cell stiffness in MCF7 cells and MDA-MB-231 cell lines and highly inhibited cell migration (39.2%) in MCF-7 and (38.6%) in MDA-MB-231 cell lines through the GO nanosheets-mediated disruption of the intracellular cytoskeleton. In the presence of GO nanosheets, the cell migration of both cell lines, as well as the cell stiffness, significantly decreased. Moreover, after GO nanosheets treatment, the cell actin network dramatically changed. The experimental and theoretical approaches established a quantitative picture of changes in these networks. Our results showed the reduction of the order parameter in actin filaments was 23% in the MCF7 cell line and 20.4% in the MDA-MB-231 cell line. The theoretical studies also showed that the GO nanosheet–actin filaments have stable interaction during MD simulation. Moreover, the 2D free energy plot indicated the GO nanosheet can induce conformational changes in actin filaments. Our findings showed that the GO nanosheets can increase the distance of actin-actin subunits from 3.22 to 3.5 nm and in addition disrupt native contacts between two subunits which lead to separate actin subunits from each other in actin filaments. In this study, the biomechanical characteristics were used to explain the effect of GO nanosheets on cells which presents a novel view of how GO nanosheets can affect the biological properties of cells without cell death. These findings have the potential to be applied in different biomedical applications.
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