Combined effects of microtopography and cyclic strain on vascular smooth muscle cell orientation

Abstract

Cellular alignment studies have shown that cell orientation has a large effect on the expression and behavior of cells. Cyclic strain and substrate microtopography have each been shown to regulate cellular alignment. This study examined the combined effects of these two stimuli on the alignment of bovine vascular smooth muscle cells (VSMCs). Cells were cultured on substrates with microgrooves of varying widths oriented either parallel or perpendicular to the direction of an applied cyclic tensile strain. We found that microgrooves oriented parallel to the direction of the applied strain limited the orientation response of VSMCs to the mechanical stimulus, while grooves perpendicular to the applied strain enhanced cellular alignment. Further, the extent to which parallel grooves limited cell alignment was found to be dependent on the groove width. It was found that for both a small (15microm) and a large (70microm) groove width, cells were better able to reorient in response to the applied strain than for an intermediate groove width (40microm). This study indicates that microtopographical cues modulate the orientation response of VSMCs to cyclic strain. The results suggest that there is a range of microgroove dimensions that is most effective at maintaining the orientation of the cells in the presence of an opposing stimulus induced by cyclic strain.

Molecular differentiation and specialization of vascular beds

“…Vascular smooth muscle cell (VSMC) coverage is more pronounced on arteries and circumferential alignment of these cells (perpendicular to the direction of blood flow) is likely to maximize structural support given to the endothelium [29][30][31]. Certain smooth muscle differentiation markers, like the protein smoothelin which also directly contributes to contractility, are expressed in VSMCs of perinatal arteries but not in veins [32,33].…”

Automated and Adaptable Quantification of Cellular Alignment from Microscopic Images for Tissue Engineering Applications

“…Various approaches have been developed to align cells, including topographical pattern (e.g., microgrooves), 16,17 mechanical stimulation (e.g., shear stress, 11 cyclic tension, and combined stimulation), 20 electrical stimulation, 21 and bioprinting. [22][23][24][25][26][27] Quantification of cellular alignment is necessary to validate the effectiveness of these approaches and the engineered microenvironment.…”

“…Although quantification of cellular alignment by measuring its physical consequences (e.g., mechanical anisotropy or polarization of infrared light) have been achieved before, 28 this is generally performed in the laboratories primarily by analyzing microscope images using manual measurements 29,30 or automated methods. 11,31,32 Although manual measurement is reliable, 33 it suffers from several limitations: (i) it is tedious and time consuming, (ii) the processing efficiency is low especially when multiple images with hundreds of cells are needed to be processed, and (iii) it has interoperator variability.…”

Influence of Extracellular Matrix Proteins and Substratum Topography on Corneal Epithelial Cell Alignment and Migration

“…The modulation of cellular behavior and differentiation by soluble factors, 15,[36][37][38][39] surface chemistry, [40][41][42][43][44] and biophysical attributes of the extracellular microenvironment [45][46][47][48] has been well established. While, the majority of studies have investigated only one type of biophysical or chemical cue in isolation, a limited number have explored the interaction between multiple biophysical cues, 11,49 surface chemistry, 19,50 or soluble cytoactive factors. 15 Here we have demonstrated that the simultaneous presentation of substratum topographic cues and surfaceassociated biochemical cues potently modulated cellular behavior.…”