Cell orientation response to cyclically deformed substrates: experimental validation of a cell model

Abstract

We have developed a stochastic model that describes the orientation response of bipolar cells grown on a cyclically deformed substrate. The model was based on the following hypotheses regarding the behavior of individual cells: (a) the mechanical signal responsible for cell reorientation is the peak to peak surface strain along the cell's major axis (p-p axial strain); (b) each cell has an axial strain threshold and the threshold is normally distributed in the cell population; (c) the cell will avoid any direction where the p-p axial strain is above its threshold; and (d) the cell will randomly orient within the range of directions where the p-p axial strains are less than the cell's threshold. These hypotheses were tested by comparing model predictions with experimental observations from stretch experiments conducted with human melanocytes. The cells were grown on elastic rectangular culture dishes subjected to unidirectional cyclic (1 Hz) stretching with amplitudes of 0, 4, 8, and 12%. After 24 h of stimulation, the distribution of cell orientations was determined by measuring the orientations of 300-400 randomly selected cells. The 12% stretch experiment was used to determine the mean, 3.5%, and the standard deviation, 1.0% of the strain threshold for the cell population. The Kolmogorov-Smirnov test was then used to determine if the orientation distributions predicted by the model were different from experimentally measured distributions for the 4 and 8% stretches. No significant differences were found between the predicted and experimental distributions (4%: p = 0.70; and 8%: p = 0.71). These results support the hypothesis that cells randomly orient, but avoid directions where the p-p axial strains are above their thresholds.