Morphogenetic response of cultured normal and transformed fibroblasts, and epitheliocytes, to a cylindrical substratum surface Possible role for the actin filament bundle pattern

Abstract

Morphometric characteristics such as cell area, dispersion, elongation and orientation were studied in normal and transformed fibroblasts, and in epitheliocytes cultured on flat or cylindrical substrata. Cylindrical surfaces with a high degree of curvature (12-13 or 25 microns radii) were shown to affect cell size, shape and alignment. The reaction of the cells to the curvature of cylindrical substrata was different in various cell types studied and depended on the pattern of actin microfilament bundles. The cells containing pronounced straight actin bundles (mouse embryo fibroblasts at the polarization stage of spreading, single spread cells of the ‘normal’ epithelial FBT line or the fully transformed epithelial IAR 6–1 line) were relatively resistant to bending around a cylindrical substratum, and became elongated and oriented along the cylinder. Cells with circular actin bundles as the predominant pattern (mouse embryo fibroblasts at the radial stage of spreading, single spread cells of ‘normal’ epithelial IAR 20 line) and cells with insufficient or no actin bundles (transformed fibroblastic L line) were prone to bending around a cylinder with much less pronounced elongation and orientation along its axis. The data obtained indicate that the reaction of cultured cells to the geometry of the substratum surface and, in particular, to a cylindrical surface is determined not only by the presence or absence of actin microfilament bundles but by their pattern in the cell.

Curvature and Rho activation differentially control the alignment of cells and stress fibers

“…1B). This method generates a more accurate representation of cell morphology on the cylinder surface than a projection normal to the cylinder axis (8)(9)(10)(11).…”

“…Less is known about how larger geometric cues (that is, those on the order of a cell length scale) influence cell behaviors. When cultured on cylinders with radii less than or equal to the cell length scale, fibroblasts align their nuclei (8), cell bodies (9,10), and stress fibers (SFs) (originally referred to as actin bundles) (11) in the axial direction. On cylinders with radii larger than cell length scales, this preferential orientation is lost (8,10).…”

“…It has been hypothesized that SFs and thus cell bodies align in the axial direction because this orientation minimizes the energetic costs associated with SF bending. Epithelial cells cultured on cylinders with small radii have SFs aligned in the circumferential direction, that is, the direction orthogonal to the SF alignment direction in fibroblasts (9,11,12). Thus, the mechanisms driving alignment cannot be simply explained by substrate geometry.…”

Passive control of cell locomotion using micropatterns: the effect of micropattern geometry on the migratory behavior of adherent cells

“…were designed to explore whether cells aligned along the anisotropic direction irrespective of micro or nanoscale. [24][25][26][27][28][29][30][31] The anisotropic topographical patterns were successful to enhance and suppress cell alignment along and across them, respectively. However, their success was still far from fully controlling cell locomotion (e.g., direction and rate of cell migration).…”

Probing cell shape regulation with patterned substratum: requirement of myosin II-mediated contractility

“…While direct evidence is lacking, this active mechanism is supported by the ability of a cell to retract its trailing end during migration, 5 and to minimize bending as demonstrated by the preferential longitudinal alignment on cylindrical surfaces. 6,7 Previous studies have used patterned substrata to probe the responses of cells to different shapes imposed by adhesive reactions. 8,9 These results demonstrated the ability of cells to adapt to square and circular shapes, and to straddle multiple adhesive regions within certain distances.…”