[show abstract][hide abstract] ABSTRACT: Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography.
PLoS ONE 01/2012; 7(5):e34830. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: B-lymphocyte activation plays an important role in humoral immune system, and its process has been studied well in vivo and in vitro. However, the ultrastructure and adhesion property changes remain unclear. In this study, changes in the morphology and mechanical properties of human peripheral blood B lymphocytes were first studied by atomic force microscopy (AFM). B lymphocytes were treated with the mitogen, pokeweed mitogen (PWM), and Staphylococcus aureus Cowan strain I (SAC) for 24 hr. After B lymphocyte is stimulated by the mitogen, the cell height, diameter, and volume are changed in different degree. The ultrastructure of the B lymphocytes membrane obviously displayed proteins gathering, corresponding with larger changes of average roughness and mean height of particles on cell membrane. Meanwhile, we detected the adhesion force of B lymphocytes after being stimulated by PWM and SAC. We found that the treated cells had a higher adhesion force of 304.16 ± 60.30 pN (PWM) and 249.63 ± 58.03 pN (SAC) than that of control group (104.28 ± 21.77 pN). Therefore, our results could provide new information to further understand the B-lymphocyte activation process and their structure-function analyses.
[show abstract][hide abstract] ABSTRACT: The cell surface glycoprotein CD44 was implicated in the progression, metastasis and apoptosis of certain human tumors. In this study, we used atomic force microscope (AFM) to monitor the effect of curcumin on human hepatocellular carcinoma (HepG2) cell surface nanoscale structure. High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with curcumin. The membrane average roughness increased (10.88 ± 4.62 nm to 129.70 ± 43.72 nm) and the expression of CD44 decreased (99.79 ± 0.16% to 75.14 ± 8.37%). Laser scanning confocal microscope (LSCM) imaging showed that CD44 molecules were located on the cell membrane. The florescence intensity in control group was weaker than that in curcumin treated cells. Most of the binding forces between CD44 antibodies and untreated HepG2 cell membrane were around 120-220 pN. After being incubated with curcumin, the major forces focused on 70-150 pN (10 μM curcumin-treated) and 50-120 pN (20 μM curcumin-treated). These results suggested that, as result of nanoscale molecular redistribution, changes of the cell surface were in response to external treatment of curcumin. The combination of AFM and LSCM could be a powerful method to detect the distribution of cell surface molecules and interactions between molecules and their ligands.
[show abstract][hide abstract] ABSTRACT: The pathological changes of erythrocytes were detected at the nanometer scale, which was important for revealing the onset of diseases, early diagnosis, and effective therapies. Diseases may disturb the morphology and function of erythrocytes at molecular scale. There were dramatic surface deformations in topography of erythrocytes from a patient with elliptocytosis complicating idiopathic thrombocytopenic purpura (ITP). The overall shape and surface membrane of the healthy, pre- and post-therapeutic erythrocytes have been studied by high-resolution atomic force microscopy imaging. The results showed that we can detect healthy and pathological erythrocytes by the morphologic parameters of the length, width, ratio of length to width, peak, valley, valley-to-peak, surface fluctuation, and standard deviations of the erythrocytes. Therefore, the morphologic information of erythrocytes is very important indictor for diagnosing the healthy and disease, as well as evaluating therapeutic effect.
[show abstract][hide abstract] ABSTRACT: The photodynamic antimicrobial chemotherapy as a promising approach for efficiently killing pathogenic microbes is attracting increasing interest. In this study, the cytotoxic and phototoxic effects of hematoporphyrin monomethyl ether (HMME) on the Gram-positive and Gram-negative bacteria were investigated. The cell viability was assessed by colony-forming unit method, and the results indicated that there was no significant cytotoxicity but high phototoxicity in the examined concentrations. Notably, the Gram-positive bacteria were more sensitive to HMME in phototoxicity. Simultaneously, an atomic force microscope (AFM) was used to detect the changes in morphological and nanomechanical properties of bacteria before and after HMME treatment. AFM images indicate that upon photoinactivation, the bacterial surface changed from a smooth, homogeneous architecture to a heterogenous, crackled morphology. The force spectroscopy measurements reveal that the cell wall became less rigid and the Young's modulus decreased about 50%, whereas the tip-cell-surface adhesion forces increased significantly compared to those of native cells. It was speculated that the photodynamic effects of HMME induced the changes in the chemical composition of the outer membrane and exposure of some proteins inside the envelope. AFM can be utilized as a powerful and sensitive method for studying the interaction between bacteria and drugs.
Applied Microbiology and Biotechnology 10/2010; 88(3):761-70. · 3.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mechanical properties of cells are important for many cellular processes. Here, atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) were carried out to characterize lymphocyte and Jurkat cells. The average elastic modulus of lymphocyte is 1.24 +/- 0.09 kPa, which is almost twofold higher than that of Jurkat cell (0.51 +/- 0.06 kPa). LSCM images of sub-membrane cytoskeleton showed a significant difference in the organization of their F-actin structures. Lymphocyte cells had more and thicker actin bundles than that of Jurkat cells. Lymphocyte and Jurkat cells after adding the F-actin destabilizing agent Cytochalasin-B (Cyt-B) were also investigated by AFM. A decrease in the elastic modulus of lymphocyte from a value of 1.24 +/- 0.09 kPa down to 0.34 +/- 0.04 kPa for 24 h was observed, and that of Jurkat cell decreased from 0.51 +/- 0.06 kPa to 0.23 +/- 0.04 kPa. We really believe that this technology will be used for cancer detection and opens a door to study the biophysical properties of signaling domains extending from the cell surface to deeper parts of the cell.
[show abstract][hide abstract] ABSTRACT: The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes. Therefore, early detection and the ability to monitor the progression of type 2 diabetes are very important for developing effective therapies. Type 2 diabetes is associated with high blood glucose in the context of insulin resistance and relative insulin deficiency. These abnormalities may disturb the architecture and functions of erythrocytes at molecular scale. In this study, the aging- and diabetes-induced changes in morphological and biomechanical properties of erythrocytes are clearly characterized at nanometer scale using atomic force microscope (AFM). The structural information and mechanical properties of the cell surface membranes of erythrocytes are very important indicators for determining the healthy, diseased or aging status. So, AFM may potentially be developed into a powerful tool in diagnosing diseases.
Biochemical and Biophysical Research Communications 01/2010; 391(4):1698-702. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Optical polymer nanofibers have highly configurable ability and good guiding properties, which are desirable for building blocks into ultracompact functional photonic devices. In this paper, a flexible and elastic enough polymer nanofiber — poly(trimethylene terephthalate) (PTT) nanofiber with low loss, fabricated by one-step drawing process, was used to building blocks into a series of ultracompact structures and microphotonic devices, such as crossed networks, nanobird's structure, coupling splitter, ring resonator, Mach-Zehnder interferometers, etc. The results show that these structures and devices are ultracompact with low loss from visible lights to near-infrared region. Therefore, the PTT nanofibers would be promising in constructing miniaturized photonic integrated circuits (PICs), which could provide significant potentials in the fields of optical communications, optical sensing, and optical manipulation.
[show abstract][hide abstract] ABSTRACT: We report a series of ultracompact photonic coupling splitters with multi-input/output ports assembled by twisting flexible polymer nanowires, which were fabricated by one-step drawing method from poly(trimethylene terephthalate) (PTT). Experimental demonstration shows that the properties of the splitters are dependent on the operation wavelength and the input branch of the optical signal launched. For a fixed operation wavelength and the input branch, desirable splitting ratio can be tuned by controlling the input/output branching angle. The excess loss of these splitters is less than 1 dB, and the intrinsic loss is less than 0.4 dB. They are desirable for high density photonic integrated circuits (PICs) and nanonetworks, while the twisting technology will be useful in constructing other wire-based photonic devices.
[show abstract][hide abstract] ABSTRACT: We report flexible and elastic enough nanofibers with diameters down to 60 nm and lengths up to 500 mm, fabricated by one-step drawing process from molten poly(trimethylene terephthalate) (PTT), exhibiting high surface smoothness and length uniformity. A series of ultracompact devices (such as optical beam splitters, couplers, rings, resonators, and tweezer/scissor-shaped structures) and nanophotonic device arrays have been assembled by the PTT nanofibers. Quantitative studies demonstrate that the PTT nanofibers/nanofiber devices exhibit good guiding properties with low optical loss from visible to near infrared region. The results suggest that the PTT nanophotonic fibers/wires would be promising candidates in constructing miniaturized photonic devices and ultracompact photonic integrated circuits (PICs), and a one-step drawing as an alternative to the standard optical bench technique.