Correlation between speed and turning naturally arises for sparsely sampled cell movements

Abstract

AbstractMechanisms regulating cell movement are not fully understood. One feature of cell movement that determines how far cells displace from an initial position is persistence, the ability to perform movements in a direction similar to the previous movement direction. Persistence is thus determined by turning angles between two sequential displacements. Recent studies found that a cell’s average speed and turning are negatively correlated, suggesting a fundamental cell-intrinsic program whereby cells with a lower turning ability (i.e., larger persistence) are intrinsically faster. Using simulations, we show that a negative correlation between the measured average cell speed and turning angle naturally arises for cells undergoing a correlated random walk due to sub-sampling, i.e., when the frequency of sampling is lower than frequency at which cells make movements. Assuming heterogeneity in persistence and intrinsic speeds of individual cells results in a negative correlation between average speed and turning angle that resembles experimentally observed correlations. Changing the frequency of imaging or calculating displacement of cohorts of cells with different speeds resulted in similar results whether or not there is a cell-intrinsic correlation between cell speed and persistence, and we could find several different parameter sets that allow to approximately match experimental data binned into cell cohorts. Interestingly, re-analysis of data of T cells in zebrafish showed that the observed correlation between persistence and speed is highly sensitive to sampling frequency, disappearing for coarsely sampled data. Our results thus challenge an established paradigm that persistent cells have intrinsically faster speeds and emphasize the role sampling frequency may have on inference of critical cellular mechanisms of cell motility.Significance StatementMeasurement of cell movements often results in a negative correlation between average speed and average turning angle, suggesting an existence of a universal, cell-intrinsic movement program. We show that such a negative correlation may arise if cells in the population differ in their ability for persistent movement when the movement data are sub-sampled. We show that such a model is consistent with the published experimental data and provide potential ways of how the sub-sampling model can be falsified.