Effects of Cyclic Stretch Waveform on Endothelial Cell Morphology Using Fractal Analysis

Abstract

Endothelial cells are remodeled when subjected to cyclic loading. Previous in vitro studies have indicated that frequency, strain amplitude, and duration are determinants of endothelial cell morphology, when cells are subjected to cyclic strain. In addition to those parameters, the current study investigated the effects of strain waveform on morphology of cultured endothelial cells quantified by fractal and topological analyses. Cultured endothelial cells were subjected to cyclic stretch by a designed device, and cellular images before and after tests were obtained. Fractal and topological parameters were calculated by development of an image-processing code. Tests were performed for different load waveforms. Results indicated cellular alignment by application of cyclic stretch. By alteration of load waveform, statistically significant differences between cell morphology of test groups were observed. Such differences are more prominent when load cycles are elevated. The endothelial cell remodeling was optimized when the applied cyclic load waveform was similar to blood pressure waveform. Effects of load waveform on cell morphology are influenced by alterations in load amplitude and frequency. It is concluded that load waveform is a determinant of endothelial morphology in addition to amplitude and frequency, and such effect is elevated by increase of load cycles. Due to high correlation between fractal and topological analyses, it is recommended that fractal analysis can be used as a proper method for evaluation of alteration in cell morphology and tissue structure caused by application of external stimuli such as mechanical loading.