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1.
Sci Rep ; 8(1): 1002, 2018 01 17.
Article in English | MEDLINE | ID: mdl-29343719

ABSTRACT

Exploration of human pulmonary artery endothelial cell (EC) as a prototypical biomechanical system has important pathophysiologic relevance because this cell type plays a key role in the development of a wide variety of clinical conditions. The complex hierarchical organization ranging from the molecular scale up to the cellular level has an intimate and intricate relationship to the barrier function between lung tissue and blood. To understand the innate molecule-cell-tissue relationship across varied length-scales, the functional role of c-Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier-altering agonists was investigated using atomic force microscopy. Concurrently, the spatially specific arrangement of cytoskeleton structure and dynamic distribution of critical proteins were examined using scanning electron microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA attenuates both thrombin- and sphingosine 1-phosphate (S1P)-mediated structural changes in ECs, specifically spatially-defined changes in elastic modulus and distribution of critical proteins. These results indicate that c-Abl kinase is an important determinant of cortical actin-based cytoskeletal rearrangement. Our findings directly bridge the gap between kinase activity, structural complexity, and functional connectivity across varied length-scales, and suggest that manipulation of c-Abl kinase activity may be a potential target for the treatment of pulmonary barrier disorders.


Subject(s)
Actin Cytoskeleton/drug effects , Endothelial Cells/drug effects , Mechanotransduction, Cellular , Proto-Oncogene Proteins c-abl/genetics , Actin Cytoskeleton/metabolism , Actin Cytoskeleton/ultrastructure , Antigens, CD/genetics , Antigens, CD/metabolism , Biomechanical Phenomena , Cadherins/genetics , Cadherins/metabolism , Cell Line , Cortactin/genetics , Cortactin/metabolism , Elastic Modulus , Endothelial Cells/metabolism , Endothelial Cells/ultrastructure , Gene Expression Regulation , Humans , Lysophospholipids/pharmacology , Microscopy, Atomic Force , Paxillin/genetics , Paxillin/metabolism , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Proto-Oncogene Proteins c-abl/metabolism , Pulmonary Artery/cytology , Pulmonary Artery/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sphingosine/analogs & derivatives , Sphingosine/pharmacology , Thrombin/pharmacology
2.
Sci Rep ; 7(1): 14152, 2017 10 26.
Article in English | MEDLINE | ID: mdl-29075042

ABSTRACT

The endothelium serves as a size-selective barrier and tightly controls the fluid exchange from the circulation to the surrounding tissues. In this study, a multiplexed microscopy characterization is developed to study the spatio-temporal effects of Abl kinases on endothelial cytoskeletal structure using AFM, SEM, and immunofluorescence. Sphingosine 1-phosphate (S1P) produces significant endothelial barrier enhancement by means of peripheral actin rearrangement. However, Abl kinase inhibition by imatinib reduces rapid redistribution of the important cytoskeletal proteins to the periphery and their association with the cortical actin ring. Herein, it moderates the thickness of the cortical actin ring, and diminishes the increase in elastic modulus at the periphery and cytoplasm. These findings demonstrate that imatinib attenuates multiple cytoskeletal changes associated with S1P-mediated endothelial barrier enhancement and suggest a novel role for Abl kinases in mediating these S1P effects. These observations bridge the gap between molecule dynamics, structure complexity and function connectivity across varied length-scales to improve our understanding on human pulmonary endothelial barrier regulation. Moreover, our study suggests a framework for understanding form-function relationships in other biomechanical subsystems, wherein complex hierarchical organization programmed from the molecular scale to the cellular and tissue levels has an intimate relationship to the overall physiological function.


Subject(s)
Cytoskeleton/drug effects , Imatinib Mesylate/pharmacology , Protein Kinase Inhibitors/pharmacology , Pulmonary Artery/cytology , Antigens, CD/metabolism , Cadherins/metabolism , Cells, Cultured , Cortactin/metabolism , Cytoskeleton/ultrastructure , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Fluorescent Antibody Technique , Humans , Lysophospholipids/pharmacology , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Paxillin/metabolism , Proto-Oncogene Proteins c-abl/agonists , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Pulmonary Artery/drug effects , Sphingosine/analogs & derivatives , Sphingosine/pharmacology
3.
Nanoscale ; 5(12): 5316-20, 2013 Jun 21.
Article in English | MEDLINE | ID: mdl-23681477

ABSTRACT

The aqueous dispersion of graphene or reduced graphene oxide (RGO) is very much important to realize the full potential of these materials in many fields. Herein we present a simple route to prepare highly water dispersible aminoclay-RGO (AC-RGO) hybrids by the in situ condensation of aminoclay over graphene oxide (GO) followed by reduction with hydrazine hydrate. The resultant hybrids are stable in aqueous media even at concentrations up to 7.5 mg RGO per mL. To the best of our knowledge this is the highest concentration of an aqueous dispersion of RGO. Significantly, the hybrids are amphiphilic in nature and show simultaneous adsorption of Cytochrome C through hydrophobic interaction and DNA through electrostatic interaction. This strategy opens up new possibilities for the prospect of RGO in catalysis and biomedical applications.


Subject(s)
Graphite/chemistry , Adsorption , Catalysis , Cytochromes c/chemistry , Cytochromes c/metabolism , DNA/chemistry , Hydrazines/chemistry , Hydrophobic and Hydrophilic Interactions , Isoelectric Point , Oxides/chemistry , Static Electricity , Water/chemistry
4.
Nano Lett ; 12(11): 5979-84, 2012 Nov 14.
Article in English | MEDLINE | ID: mdl-23072307

ABSTRACT

The morphology of crystalline precipitates in a solid-state matrix is governed by complex but tractable energetic considerations driven largely by volume strain energy minimization and anisotropy of interfacial energies. Spherical precipitate morphologies are favored by isotropic systems, while anisotropic interfacial energies give energetic preference to certain crystallographically oriented interfaces, resulting in a faceted precipitate morphology. In conventional solid-solution precipitation, a precipitate's morphological evolution is mediated by surface anchoring of capping molecules, which dramatically alter the surface energy in an anisotropic manner, thereby providing exquisite morphology control during crystal growth. Herein, we present experimental evidence and theoretical validation for the role of a ternary element (Na) in controlling the morphology of nanoscale PbS crystals nucleating in a PbTe matrix, an important bulk thermoelectric system. The PbS nanostructures formed by phase separation from a PbI(2)-doped or undoped PbTe matrix have irregular morphologies. However, replacing the iodine dopant with Na (1-2 mol %) alters dramatically the morphology of the PbS precipitates. Segregation of Na at PbTe/PbS interfaces result in cuboidal and truncated cuboidal morphologies for PbS. Using analytical scanning/transmission electron microscopy and atom-probe tomography, we demonstrate unambiguously that Na partitions to the precipitates and segregates at the matrix/precipitate interfaces, inducing morphological anisotropy of PbS precipitates. First-principles and semiclassical calculations reveal that Na as a solute in PbTe has a higher energy than in PbS and that Na segregation at a (100) PbTe/PbS interface decreases the total energy of matrix/precipitate system, resulting in faceting of PbS precipitates. These results provide an impetus for a new strategy for controlling morphological evolution in matrix/precipitate systems, mediated by solute partitioning of ternary additions.

5.
J Am Chem Soc ; 133(23): 8786-9, 2011 Jun 15.
Article in English | MEDLINE | ID: mdl-21557606

ABSTRACT

The Pb- and Sb- dual nanostructured PbTe system exhibits anomalous electronic transport behavior wherein the carrier mobility first increases and then decreases with increase in temperature. By combining in situ transmission electron microscopy observations and theoretical calculations based on energy filtering of charge carriers, we propose a plausible mechanism of charge transport based on interphase potential that is mediated by interdiffusion between coexisting Pb and Sb precipitates. These findings promise new strategies to enhance thermoelectric figure of merit via dual and multinanostructuring of miscible precipitates.

6.
J Phys Chem B ; 109(9): 3704-6, 2005 Mar 10.
Article in English | MEDLINE | ID: mdl-16851411

ABSTRACT

Supported gold catalysts have drawn worldwide interest due to the novel properties and potential applications in industries. However, the origin of the catalytic activity in gold nanoparticles is still not well understood. In this study, time-of-flight secondary ion mass spectroscopy (TOF-SIMS) has been applied to investigate the nature of gold in Au (1.3 wt %)/gamma-Al2O3 and Au (2.8 wt %)/TiO2 catalysts prepared by the deposition-precipitation method. The SIMS spectrum of the supported gold catalysts presented AuO-, AuO2-, and AuOH- ion clusters. These measurements show direct evidence for oxidized gold on supported gold catalysts and may be helpful to gaining better understanding of the origin of the catalytic activity.

7.
J Microsc ; 216(Pt 2): 194-6, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15516231

ABSTRACT

A novel repositioning approach is described for repeated observations of a specimen at a close proximal location in the atomic force microscope. The approach is similar to keystone architecture, whereby the repositioning is achieved by forming a male structured base for the specimen, and a corresponding female counterpart as the frame. For the combination of an acrylic acid frame and a metal base, 90% translation shifts are less than 10 microm, and almost all angular disorientations are within +3 degrees to -3 degrees . Nanometre-scale surface features can be relocated easily and reliably even after 40 imaging-removal-imaging cycles, dipping the specimen in solutions or heating up to 500 degrees C.


Subject(s)
Microscopy, Atomic Force/instrumentation , Microscopy, Atomic Force/methods , Nanotechnology/instrumentation , Nanotechnology/methods , Reproducibility of Results , Sensitivity and Specificity , Surface Properties
8.
Proc Natl Acad Sci U S A ; 98(13): 7113-6, 2001 Jun 19.
Article in English | MEDLINE | ID: mdl-11416196

ABSTRACT

Materials with high electrical conductivity and optical transparency are needed for future flat panel display, solar energy, and other opto-electronic technologies. In(x)Cd(1-x)O films having a simple cubic microstructure have been grown on amorphous glass substrates by a straightforward chemical vapor deposition process. The x = 0.05 film conductivity of 17,000 S/cm, carrier mobility of 70 cm2/Vs, and visible region optical transparency window considerably exceed the corresponding parameters for commercial indium-tin oxide. Ab initio electronic structure calculations reveal small conduction electron effective masses, a dramatic shift of the CdO band gap with doping, and a conduction band hybridization gap caused by extensive Cd 5s + In 5s mixing.

9.
Microsc Res Tech ; 30(3): 208-17, 1995 Feb 15.
Article in English | MEDLINE | ID: mdl-7718915

ABSTRACT

Electron energy loss spectrometry (EELS) with a cold field emission gun (cFEG) transmission electron microscope (TEM) is implemented to analyze the evolution of the electronic structure and dielectric function of oxide superconductors. The O-K core loss spectra of p-type doped oxide superconductors are analyzed in terms of holes formation on oxygen sites, while low loss spectra are analyzed for free carrier plasmas, other spectral excitations, and their crystallographic confinement. It is illustrated that the transmission EELS with a cFEG TEM very much complement soft X-ray absorption spectroscopy and optical spectroscopy, with the added advantages of high spatial resolution (approximately 1-100 nm), and is compatible with other analytical, diffraction, and imaging techniques, which are readily available in a cFEG TEM.


Subject(s)
Electric Conductivity , Oxides/chemistry , Anisotropy , Cold Temperature , Microscopy, Electron , Semiconductors
10.
Science ; 266(5182): 102-4, 1994 Oct 07.
Article in English | MEDLINE | ID: mdl-17814005

ABSTRACT

An atomic structure model for a 25 degrees [001] symmetric tilt grain boundary in SrTiO(3) has been determined directly from experimental data with the use of high-resolution Z-contrast imaging coupled with electron energy loss spectroscopy. The derived model of the grain boundary was refined by bond-valence sum calculations and reveals candidate sites for dopant atoms in the boundary plane. These results show how the combined techniques can be used to deduce the atomic structure of defects and interfaces without recourse to preconceived structural models or image simulations.

11.
Science ; 259(5101): 1601-4, 1993 Mar 12.
Article in English | MEDLINE | ID: mdl-17733027

ABSTRACT

Transmission electron microscopy (TEM) observations of graphite tubules (buckytubes) and their derivatives have revealed not only the previously reported buckytube geometries but also additional shapes of the buckytube derivatives. Detailed cross-sectional TEM images reveal the cylindrical cross section of buckytubes and the growth pattern of buckytubes as well as their derivatives. These observations of frozen growth stages of buckytubes and derivatives suggest a helical growth mechanism analogous to that of crystal growth via screw dislocations. The helicacy of buckytubes is analyzed by electron diffraction whereas the anisotropy of electronic structure is revealed by momentum transfer resolved electron energy loss spectrometry. Based on the TEM observations, it is proposed that buckytubes act as precursors to closed-shell fullerene (buckyball) formation and the possible steps in buckyball formation are outlined. In arc evaporation experiments in which residue rods (containing various amounts of buckytubes) were used as the starting anode for fullerene production, the amount of buckytubes in the rod was correlated with fullerene yield.

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