RT Journal Article SR Electronic T1 Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.20.436273 DO 10.1101/2021.03.20.436273 A1 Kotryna Vaidžiulytė A1 Anne-Sophie Macé A1 Aude Battistella A1 William Beng A1 Kristine Schauer A1 Mathieu Coppey YR 2021 UL http://biorxiv.org/content/early/2021/04/07/2021.03.20.436273.abstract AB Migrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in RPE1 cells over long timescales. By live-cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed towards protrusions with a 20 min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.Competing Interest StatementThe authors have declared no competing interest.