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At least 775 records · Page 43Linked to original sources
PubMed2001

Tumor cell adhesion under hydrodynamic conditions of fluid flow.

Current evidence indicates that tumor cell adhesion to the microvasculature in host organs during formation of distant metastases is a complex process involving various types of cell adhesion molecules. Recent results have shown that stabilization of tumor cell adhesion to the microvascular vessel wall is a very important step for successful tumor cell migration and colonization of host organs. We are beginning to understand the influences of fluid flow and local shear forces on these adhesive interactions and cellular responses within the circulation. Mechanosensory molecules or molecular complexes can transform shear forces acting on circulating tumor cells into intracellular signals and modulate cell signaling pathways, gene expression and other cellular functions. Flowing tumor cells can interact with microvascular endothelial cells mediated mainly by selectins, but the strength of these bonds is relatively low and not sufficient for stable cell adhesions. Integrin-mediated tumor cell adhesion and changes in the binding affinity of these adhesion molecules appear to be required for stabilized tumor cell adhesion and subsequent cell migration into the host organ. Failure of the conformational affinity switch in integrins results in breaking of these bonds and recirculation or mechanical damage of the tumor cells. Various cell signaling molecules, such as focal adhesion kinase, pp60src or paxillin, and cytoskeletal components, such as actin or microtubules, appear to be required for tumor cell adhesion and its stabilization under hydrodynamic conditions of fluid flow.

Animals↗
PubMed1996

Adhesion through L-selectin requires a threshold hydrodynamic shear.

Selectins are cell adhesion molecules that bind carbohydrate ligands and promote interaction between leukocytes and the vessel wall in vascular shear flow. Selectin-ligand bonds have high mechanical strength, allowing initial tethering to the vessel wall through one or few bonds, and have fast on and off rates, permitting rolling in response to hydrodynamic drag. The L-selectin molecule on leukocytes binds to peripheral node addressin on high endothelial venules of lymph nodes to mediate leukocyte rolling and binds to a ligand on neutrophils to mediate rolling of leukocytes over one another. Here we describe a surprising mechanism for regulation of these interactions, both in vitro and in vivo. Shear above a critical threshold is required to promote and maintain rolling interactions through L-selectin, but not through E-selectin, P-selectin or VCAM-1. The shear threshold requirement for L-selectin may be physiologically important in low shear to prevent inappropriate aggregation of leukocytes and interaction with the vessel wall.

Animals↗
PubMed2004

Biomechanics: hydrodynamic function of the shark's tail.

The tail of most sharks has an elongated upper lobe that differs from the externally symmetrical tail structure common among bony fishes, but the hydrodynamic purpose of this asymmetric tail shape is unclear. Here we quantify water flow patterns in the wakes of freely swimming dogfish sharks and find that they have a ring-within-a-ring vortex structure, in contrast to the single rings shed by symmetrical fish tails. The branched-ring vortex is generated by the inclined angle of the tail's trailing edge and by its motion at an angle to the horizontal body axis; the vortex directs water backwards and downwards, which may increase the shark's vertical manoeuvrability.

Animals↗
PubMed2003

Delta-wing function of webbed feet gives hydrodynamic lift for swimming propulsion in birds.

Most foot-propelled swimming birds sweep their webbed feet backwards in a curved path that lies in a plane aligned with the swimming direction. When the foot passes the most outward position, near the beginning of the power stroke, a tangent to the foot trajectory is parallel with the line of swimming and the foot web is perpendicular to it. But later in the stroke the foot takes an increasingly transverse direction, swinging towards the longitudinal axis of the body. Here we show that, early in the power stroke, propulsion is achieved mostly by hydrodynamic drag on the foot, whereas there is a gradual transition into lift-based propulsion later in the stroke. At the shift to lift mode, the attached vortices of the drag-based phase turn into a starting vortex, shed at the trailing edge, and into spiralling leading-edge vortices along the sides of the foot. Because of their delta shape, webbed feet can generate propulsive forces continuously through two successive modes, from drag at the beginning of the stroke, all the way through the transition to predominantly lift later in the stroke.

Animals↗
PubMed2003

The hydrodynamics of water strider locomotion.

Water striders Gerridae are insects of characteristic length 1 cm and weight 10 dynes that reside on the surface of ponds, rivers, and the open ocean. Their weight is supported by the surface tension force generated by curvature of the free surface, and they propel themselves by driving their central pair of hydrophobic legs in a sculling motion. Previous investigators have assumed that the hydrodynamic propulsion of the water strider relies on momentum transfer by surface waves. This assumption leads to Denny's paradox: infant water striders, whose legs are too slow to generate waves, should be incapable of propelling themselves along the surface. We here resolve this paradox through reporting the results of high-speed video and particle-tracking studies. Experiments reveal that the strider transfers momentum to the underlying fluid not primarily through capillary waves, but rather through hemispherical vortices shed by its driving legs. This insight guided us in constructing a self-contained mechanical water strider whose means of propulsion is analogous to that of its natural counterpart.

Animals↗
PubMed2006

Remodeling of the lectin-EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force.

Crystal structures of the lectin and epidermal growth factor (EGF)-like domains of P-selectin show 'bent' and 'extended' conformations. An extended conformation would be 'favored' by forces exerted on a selectin bound at one end to a ligand and at the other end to a cell experiencing hydrodynamic drag forces. To determine whether the extended conformation has higher affinity for ligand, we introduced an N-glycosylation site to 'wedge open' the interface between the lectin and EGF-like domains of P-selectin. This alteration increased the affinity of P-selectin for its ligand P-selectin glycoprotein 1 (PSGL-1) and thereby the strength of P-selectin-mediated rolling adhesion. Similarly, an asparagine-to-glycine substitution in the lectin-EGF-like domain interface of L-selectin enhanced rolling adhesion under shear flow. Our results demonstrate that force, by 'favoring' an extended selectin conformation, can strengthen selectin-ligand bonds.

Animals↗
PubMed2006

Inhibition of angiogenesis and tumor progression by hydrodynamic cotransfection of angiostatin K1-3, endostatin, and saxatilin genes.

In vivo expression of angiostatin and endostatin, two different types of endothelial cell growth inhibitor, have been reported to inhibit vascularization in tumor tissues, resulting in tumor growth inhibition. Recently, in vivo expression of saxatilin, a novel disintegrin purified from snake (Gloydius saxatilis) venom, was able to strongly inhibit endothelial cell proliferation and smooth muscle cell migration, resulting in tumor growth inhibition. However, the antitumor efficacy of the individual antiangiogenic molecules expressed in vivo was not sufficiently potent to induce tumor regression in animal models. Therefore, in this study, we have systemically examined how combinational transfer of angiostatin, endostatin, and saxatilin genes affects neovascularization in tumor tissues and tumor progression in a mouse model. In Matrigel-implanted mice, cotransfection with plasmids encoding angiostatin K1-3 (pFLAG-Angio K1/3), endostatin (pFLAG-Endo), and saxatilin (pFLAG-Sax) resulted in the most effective inhibition of angiogenesis. In addition, hydrodynamic cotransfection of the three genes induced more inhibition of B16BL6 melanoma growth and pulmonary metastasis than other combinations of transfected genes. Compared with the empty vector-treated control group, cotreatment with the three plasmids reduced B16BL6 tumor growth by 89% and pulmonary metastasis by 90%. These results provide additional evidence supporting the combined systemic expression of antiangiogenic factors, such as angiostatin K1-3, endostatin, and saxatilin, as an alternative procedure for antiangiogenic cancer therapy.

Angiogenesis Inhibitors↗
PubMed1999

Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA.

Development of methods that allow an efficient expression of exogenous genes in animals would provide tools for gene function studies, treatment of diseases and for obtaining gene products. Therefore, we have developed a hydrodynamics-based procedure for expressing transgenes in mice by systemic administration of plasmid DNA. Using cDNA of luciferase and beta-galactosidase as a reporter gene, we demonstrated that an efficient gene transfer and expression can be achieved by a rapid injection of a large volume of DNA solution into animals via the tail vein. Among the organs expressing the transgene, the liver showed the highest level of gene expression. As high as 45 microg of luciferase protein per gram of liver can be achi- eved by a single tail vein injection of 5 microg of plasmid DNA into a mouse. Histochemical analysis using beta-galactosidase gene as a reporter reveals that approximately 40percent of hepatocytes express the transgene. The time-response curve shows that the level of transgene expression in the liver reaches the peak level in approximately 8 h after injection and decreases thereafter. The peak level of gene expression can be regained by repeated injection of plasmid DNA. These results suggest that a simple, convenient and efficient method has been developed and which can be used as an effective means for studying gene function, gene regulation and molecular pathophysiology through gene transfer, as well as for expressing proteins in animals.

Animals↗
PubMed2003

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats.

Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

Animals↗
PubMed2003

Long-term therapeutic levels of human alpha-1 antitrypsin in plasma after hydrodynamic injection of nonviral DNA.

The transfection efficacy of several vectors containing the full genomic hAAT gene with its natural promoter (pTG7101) and others containing the cDNA of hAAT gene driven by cytomegalovirus immediate-early promoter or the 0.5 kb upstream of hAAT gene sequence has been studied by hydrodynamic tail-vein injection (20 microg/mouse). pTG7101 (but not the other plasmids) results in therapeutic and stable concentration of hAAT in plasma. A dose-response study with this plasmid (0.3-320 microg/mouse) confirms that hAAT remains long-term stable in plasma, with therapeutic concentrations of hAAT (>0.9 mg/ml). The parameters of the dose-response curve were: R: 0.98, E(max) 3449.0+/- 279.7 microg/ml and EC(50) 1.2 x 10(12) plasmid-gene units. In addition, 4 months after transfection, the intrinsic efficacy of transgenic expression (amount of RNA/DNA) in mouse liver was 50-80% that normally expressed by the mouse gene. The important efficacy of nonviral genomic DNA opens a new avenue in the safety applications of human gene therapy.

Animals↗
PubMed2001

Hydrodynamic characteristics and mixing behaviour of Sclerotium glucanicum culture fluids in an airlift reactor with an internal loop used for scleroglucan production.

The filamentous fungus, Sclerotium glucanicum NRRL 3006, was cultivated in a 0.008 m(3) airlift bioreactor with internal recirculation loop (ARL-IL) for production of the biopolymer, scleroglucan. The rheological behaviour of the culture fluid was characterised by measurement of the fluid consistency coefficient (K) and the flow behaviour index (n). Based on these measurements, the culture fluid changed from a low viscosity Newtonian system early in the process, to a viscous non-Newtonian (pseudoplastic) system. In addition, reactor hydrodynamics and mixing behaviour were characterised by measurement of whole mean gas hold-up (epsilon(g)), liquid re-circulation velocity (U(ld)) and mixing time (t(m)). Under identical process conditions, the effects of the viscosity of the culture fluid and air flow rate on epsilon(g), U(ld) and t(m) were examined and empirical correlations for epsilon(g), U(ld) and t(m) with both superficial velocity U(g) and consistency coefficient K were obtained and expressed separately. The correlations obtained are likely to describe the behaviour of real fungal culture fluids more accurately than previous correlations based on Newtonian or simulated non-Newtonian systems.

Ascomycota↗
PubMed1997

Speciation of selenium and arsenic compounds by capillary electrophoresis with hydrodynamically modified electroosmotic flow and on-line reduction of selenium(VI) to selenium(IV) with hydride generation inductively coupled plasma mass spectrometric detection.

Capillary electrophoresis (CE) with hydride generation inductively coupled plasma mass spectrometry was used to determine four arsenicals and two selenium species. Selenate (SeVI) was reduced on-line to selenite (SeIV) by mixing the CE effluent with concentrated HCl. A microporous PTFE tube was used as a gas-liquid separator to eliminate the 40Ar37Cl and 40Ar35Cl interference from 77Se and 75As, respectively. The direction of the electroosmotic flow during CE was reversed with hydrodynamic pressure, which allowed increased freedom of buffer choice. For conventional pressure injection, method detection limits for SeIV and SeVI based on seven replicate injections were 10 and 24 pg, respectively. Recoveries of SeIV and SeVI in drinking water were measured.

Arsenicals↗
PubMed2003

Electro-hydrodynamic micro-fluidic mixer.

Fluid mixing in microchannels is needed for many applications ranging from bio-arrays to micro-reactors, but is typically difficult to achieve. A simple geometry micro-mixer is proposed based on the electro-hydrodynamic (EHD) force present when the fluids to be mixed have different electrical properties and are subjected to an electric field. The electrodes are arranged so that the electric field is perpendicular to the interface between the two fluids, creating a transversal secondary flow. The technique is demonstrated experimentally using the flow of two liquids with identical viscosity and density, but different electrical properties. The volume flow rate and average velocity are 0.26 microl s(-1) and 4.2 mm s(-1), respectively, corresponding to a Reynolds number Re= 0.0174. The effect of a continuous (DC) electric field and two alternating (AC)- sinusoidal and square - electric fields is explored. At the appropriate parameter values, very good mixing takes place in less than 0.1 s, over a very short distance (within a fraction of the width 250 microm of the electrodes).

Journal Article↗
PubMed2004

Hydrodynamic control of the interface between two liquids flowing through a horizontal or vertical microchannel.

We derive a Fourier expansion for estimating laminar hydrodynamic spreading when two immiscible liquids flow steadily, side by side, at low Reynolds number, in a horizontal microchannel of rectangular cross-section. When the aspect ratio of the height of the channel to its width is small this expansion can be truncated after a couple of terms and solved to yield the steady-state position of the boundary in terms of the constant volumetric flow rates, the aspect ratio and the viscosities of the two liquids. Our formula shows that we can control the location of the liquid boundary at the outlet of the microchannel by adjusting the relative volumetric flow rates of the two inlet streams. If the microchannel is oriented vertically and the volumetric flow rates are very low, the position of the boundary is also influenced by gravitational forces that depend on the relative densities of the two liquids. We have tested solutions to our analytical expansions by running computational fluid dynamics simulations and have found excellent agreement. When the aspect ratio is 0.01 the leading term in the Fourier expansion for the spreading has an accuracy of about 1%. This accuracy deteriorates to about 12% when the aspect ratio is 0.1. An understanding of these spreading mechanisms is fundamental to the design of T-sensors and related microfluidic devices.

Journal Article↗
PubMed2004

Syntheses of 11C- and 18F-labeled carboxylic esters within a hydrodynamically-driven micro-reactor.

Carboxylic esters were successfully labeled with one of two short-lived positron-emitters, carbon-11 or fluorine-18, within a hydrodynamically-driven micro-reactor. The non-radioactive methyl ester was obtained at room temperature; its yield increased with higher substrate concentration and with reduced infusion rate. Radioactive methyl ester was obtained from the reaction of (10 mM) with in 56% decay-corrected radiochemical yield (RCY) at an infusion rate of 10 microL min(-1), and when the infusion rate was reduced to 1 microL min(-1), the RCY increased to 88%. The synthesis of the non-radioactive fluoroethyl ester from and required heating of the micro-reactor on a heating block at 80 degrees C (14-17% RCY), whilst the corresponding radioactive from and was obtained in 10% RCY. The radioactive 'peripheral' benzodiazepine receptor ligand was obtained from the reaction of acid with labeling agent in 45% RCY at an infusion rate of 10 microL min(-1). When the infusion rate was reduced to 1 microL min(-1), the RCY increased to 65%. The results exemplify a new methodology for producing radiotracers for imaging with positron emission tomography that has many potential advantages, including a requirement for small quantities of substrates, enhanced reaction, rapid reaction optimisation and easy product purification.

Carbon Dioxide↗
PubMed2005

Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics.

We propose here a new method for continuous concentration and classification of particles in microfluidic devices, named hydrodynamic filtration. When a particle is flowing in a microchannel, the center position of the particle cannot be present in a certain distance from sidewalls, which is equal to the particle radius. The proposed method utilizes this fact, and is performed using a microchannel having multiple side branch channels. By withdrawing a small amount of liquid repeatedly from the main stream through the side channels, particles are concentrated and aligned onto the sidewalls. Then the concentrated and aligned particles can be collected according to size through other side channels (selection channels) in the downstream of the microchannel. Therefore, continuous introduction of a particle suspension into the microchannel enables both particle concentration and classification at the same time. In this method, the flow profile inside a precisely fabricated microchannel determines the size limit of the filtered substances. So the filtration can be performed even when the channel widths are much larger than the particle size, without the problem of channel clogging. In this study, concentrations of polymer microspheres with diameters of 1-3 microm were increased 20-50-fold, and they were collected independently according to size. In addition, selective enrichment of leukocytes from blood was successfully performed.

Cell Separation↗
PubMed2005

On-chip magnetic bead microarray using hydrodynamic focusing in a passive magnetic separator.

Implementing DNA and protein microarrays into lab-on-a-chip systems can be problematic since these are sensitive to heat and strong chemicals. Here, we describe the functionalization of a microchannel with two types of magnetic beads using hydrodynamic focusing combined with a passive magnetic separator with arrays of soft magnetic elements. The soft magnetic elements placed on both sides of the channel are magnetized by a relatively weak applied external magnetic field (21 mT) and provide magnetic field gradients attracting magnetic beads. Flows with two differently functionalized magnetic beads and a separating barrier flow are introduced simultaneously at the two channel sides and the centre of the microfluidic channel, respectively. On-chip experiments with fluorescence labeled beads demonstrate that the two types of beads are captured at each of the channel sidewalls. On-chip hybridization experiments show that the microfluidic systems can be functionalized with two sets of beads carrying different probes that selectively recognize a single base pair mismatch in target DNA. By switching the places of the two types of beads it is shown that the microsystem can be cleaned and functionalized repeatedly with different beads with no cross-talk between experiments.

Magnetics↗
PubMed2006

Experimental characterization of hydrodynamic dispersion in shallow microchannels.

Hydrodynamic dispersion in shallow microchannels with almost parabolic cross-sectional shapes and with heights much less than their widths is studied experimentally. Both long serpentine channels and rotary mixers are used. The experimental results demonstrate that the dispersion depends on the width rather than the height of the channel. The results are in quantitative agreement with a recently proposed theory of dispersion in shallow channels.

Journal Article↗