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Biomedical subjects

Adam Curtis

Publications and source records attributed to Adam Curtis.

9 recordsLinked to original sources

Orthogonal (transverse) arrangements of actin in endothelia and fibroblasts.

Though actin filaments running across the cell (transverse actin) have been occasionally reported for epithelial cells in groups and for cells growing on fibres, there has been no report heretofore of transverse actin in cells grown on planar substrata. This paper describes evidence in support of this possibility derived from actin staining, polarization microscopy and force measurements. The paper introduces two new methods for detecting the orientation and activity of contractile elements in cells. The orthogonal actin is most obvious in cells grown on groove ridge structures, but can be detected in cells grown on flat surfaces.

Actins↗

Measuring cell forces by a photoelastic method.

A new method for measuring the mechanical forces exerted by cells on the substratum and through the substratum to act on other cells is described. This method depends upon the growth of cells on a photoelastic substratum, polydimethylsiloxane coated with a near monolayer of fibronectin. Changes in the forces applied by the cells to the substratum lead to changes in birefringence, which can be measured and recorded by the Polscope computer-controlled polarizing microscope. The changes in azimuth and retardance can be measured. A method for calibrating the stress is described. The method is sensitive down to forces of 1 pN per square microns. Fairly rapid changes with time can be recorded with a time resolution of approximately 1 s. The observations show that both isolated adhering, spread cells and also cells close to contact exert stresses on the substratum and that the stresses are those that would be produced by forces of 10-1000 pN per cell. The forces are almost certainly exerted on nearby cells since movement of one cell causes strains to appear around other nearby cells. The method has the defect that strains under the cells, though detectable in principle, are unclear due to birefringence of the components of the cytoplasm and nucleus. It is of special interest that the strains on the substratum can change in the time course of a few seconds and appear to be concentrated near the base of the lamellopodium of the cell as though they originated there. As well as exerting forces on the substratum in the direction of the long axis of the cell, appreciable forces are exerted from the lateral sides of the cell. The observations and measurements tend to argue that microtopography and embedded beads can concentrate the forces.

Cell Adhesion↗

Cell forces in tissues.

This articles reviews the measurement, the effects and the biological importance of forces that cells exert on each other. It does not review the effects of forces originating from movement of tissues, muscular activity, movement and gravity.

Cell Adhesion↗

Single dose of inducible nitric oxide synthase inhibitor induces prolonged inflammatory cell accumulation and fibrosis around injured tendon and synovium.

The aim of the current study was to investigate the effect of inhibition of nitric oxide (NO) production after injury on inflammatory cell accumulation and fibrosis around digital flexor tendon and synovium. A standard crush injury was applied to the flexor tendons of the middle digit of the hindpaw and the overlying muscle and synovium of female Wistar rats. Thirty animals received an intraperitoneal injection of either isotonic saline or N(G)-nitro-l-arginine methyl ester (L-NAME; 5 mg/kg) immediately following the crush injury, and five animals were then sacrificed at various intervals and the paws processed for histology. Another group of five animals was sacrificed after 3 days for nitrite determinations. The results showed that nitrite production and hence NO synthase activity is doubled at the acute phase of tendon wound healing, and we can prevent this by administering a single dose of L-NAME immediately after injury. The incidence and severity of fibrocellular adhesions between tendon and synovium was much more marked in animals treated with L-NAME. Treatment with L-NAME elicited a chronic inflammatory response characterised by a persistent and extraordinarily severe accumulation of large numbers of inflammatory cells in the subcutaneous tissues, in muscle and in tendon. These findings indicate that in the case of injured tendon and synovium, NO could act to protect the healing tissue from an uncontrolled inflammatory response.

Animals↗

A parallel-plate flow chamber to study initial cell adhesion on a nanofeatured surface.

Cells in the human body come across many types of information, which they respond to. Both material chemistry and topography of the surface where they adhere have an effect on cell shape, proliferation, migration, and gene expression. It is possible to create surfaces with topography at the nanometric scale to allow observation of cell-topography interactions. Previous work has shown that 100-nm-diameter pits on a 300-nm pitch can have a marked effect in reducing the adhesion of rat fibroblasts in static cultures. In the present study, a flow of cell suspension was used to investigate cell adhesion onto nanopits in dynamic conditions, by means of a parallel-plate flow chamber. A flow chamber with inner nanotopography has been designed, which allows real-time observation of the flow over the nanopits. A nanopitted pattern was successfully embossed into polymethylmethacrylate to meet the required shape of the chamber. Dynamic cell adhesion after 1 h has been quantified and compared on flat and nanopitted polymethylmethacrylate substrates. The nanopits were seen to be significantly less adhesive than the flat substrates (p < 0.001), which is coherent with previous observations of static cultures.

Animals↗

Tutorial on the biology of nanotopography.

The aims of this short tutorial are fourfold: 1) to introduce readers unfamiliar with the field to major concepts in the field; 2) to inform the reader of major unresolved questions; 3) to inform readers of a few major sources of relevant literature; and 4) to place the subject in relation to its relevance to other areas of science and practical application.

Animals↗

Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis.

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging contrast agents or in drug delivery applications. Tissue and cell-specific drug targeting by these nanoparticles can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. In this study, superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared and coupled to insulin for their targeting to cell expressed surface receptors and thereby preventing the endocytosis. The influence of these nanoparticles on human fibroblasts is studied using various techniques to observe cell-nanoparticle interaction that includes light, scanning, and transmission electron microscopy studies. The derivatization of the nanoparticle surface with insulin-induced alterations in cell behavior that were distinct from the underivatized nanoparticles suggests that cell response can be directed via specifically engineered particle surfaces. The results from cell culture studies showed that the uncoated particles were internalized by the fibroblasts due to endocytosis, which resulted in disruption of the cell membrane. In contradiction, insulin-coated nanoparticles attached to the cell membrane, most likely to the cell-expressed surface receptors, and were not endocytosed. The presence of insulin on the surface of the nanoparticles caused an apparent increase in cell proliferation and viability. One major problem with uncoated nanoparticles has been the endocytosis of particles leading to irreversible entry. These results provide a route to prevent this problem. The derivatized nanoparticles show high affinity for cell membrane and opens up new opportunities for magnetic cell separation and recovery that may be of crucial interest for the development of cellular therapies.

Cell Adhesion↗