A Perturbation Analysis to Understand the Mechanism How Migrating Cells Sense and Respond to a Topography in the Extracellular Environment.

Migrating cells in vivo monitor the physiological state of an organism by integrating the physical as well as chemical cues in the extracellular microenvironment, and alter the migration mode, in order to achieve their unique function. The clarification of the mechanism focusing on the topographical cues is important for basic biological research, and for biomedical engineering specifically to establish the design concept of tissue engineering scaffolds. The aim of this study is to understand how cells sense and respond to the complex topographical cues in vivo by exploring in vitro analyses to complex in vivo situations in order to simplify the issue. Since the intracellular mechanical events at subcellular scales and the way of the coordination of these events are supposed to change in the migrating cells, a key to success of the analysis is a mechanical point of view with a particular focus of the subcellular mechanical events. We designed an experimental platform to explore the mechanical requirements in a migrating fibroma cell responding to micro-grooves. The micro-grooved structure is a model of gap structures, typically seen in the microenvironments in vivo. In our experiment, the contributions of actomyosin force generation can be spatially divided and analyzed in the cell center and peripheral regions. The analysis specified that rapid leading edge protrusion, and the cell body translocation coordinated with the leading edge protrusion are required for the turning response at a micro-groove.

Characteristics of motility-based filtering of adherent cells on microgrooved surfaces.

Topographical features are known to physically affect cell behavior and are expected to have great potential for non-invasive control of such behavior. To provide a design concept of a microstructured surface for elaborate non-invasive control of cell migration, we systematically analyzed the effect of microgrooves on cell migration. We fabricated silicon microstructured surfaces covered with SiO(2) with microgrooves of various sizes, and characterized the behavior of cells moving from the flat surface to the grooved surface. The intersecting microgrooves with well-defined groove width absorbed or repelled cells precisely according to the angle of approach of the cell to the boundary with the grooved surface. This filtering process was explained by the difference in the magnitude of the lamellar dragging effect resulting from the number of the grooves interacting with the lamella of the cell. This study provides a framework to tailor the microgrooved surface for non-invasive control of cell migration with label-free detection of a specific property of the target cells. This should offer significant benefits to biomedical research and applications.

Control of highly migratory cells by microstructured surface based on transient change in cell behavior.

Cell migration control techniques have been proposed for cells with relatively low migratory activity, based on static analyses performed with cells that attain a temporally homogenous state after being exposed to a cell guiding stimulus. To elucidate new functions of substrate topography, we investigated the transient change in the behavior of highly migratory cells coming from a flat surface to a grooved surface on a silicon substrate covered with SiO(2). A single line groove (1.5 µm in width, 20 µm in depth) and intersecting grooves (1.5 µm in width, 5 µm in spacing, 20 µm in depth) functioned as an effective cell repellent. In the case of wider grooves, a single line groove (4 µm in width; 20 µm in width) had no specified function. In contrast, intersecting grooves (4 µm in width, 5 µm in spacing) functioned as a trap for the cells. Our findings yield a new design concept of cell repelling and trapping surfaces which are applicable to cell guiding methods and single or multiple cell confinement on cell culture substrates, and thus may contribute to development of more advanced biomaterials.

Thin-film fabrication method for organic light-emitting diodes using electrospray deposition.

A new method for fabricating micropatterns of MEH-PPV thin films with surface roughnesses below 1nm is proposed, using electrospray deposition and a dual-solvent technique. The basic concept is that nanoparticles are deposited on the target substrate just before they become completely dry, by adding a solvent that has an evaporation speed relatively lower than that of the original solution.