title: Steering cell migration by alternating blebs and actin-rich protrusions.
abstract: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood.
  
  
  
  Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision.
  
  
  
  Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany. alba.dizmunoz@embl.de.|International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland. alba.dizmunoz@embl.de.|Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany. alba.dizmunoz@embl.de.
authors: Alba
authors: 0000-0001-6864-8901
authors: A
authors: Diz-Muñoz
authors: Max Planck Institute for the Physics of Complex Systems, Dresden, 01187, Germany. pawel.romanczuk@hu-berlin.de.|Department of Biology, Institute of Theoretical Biology, Humboldt University, Berlin, 10115, Germany. pawel.romanczuk@hu-berlin.de.
authors: Pawel
authors: P
authors: Romanczuk
authors: Institute of Molecular and Cell Biology, A-STAR, Singapore, 138673, Singapore.
authors: Weimiao
authors: W
authors: Yu
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany.|International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.|Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany.|Medical Research Council Laboratory for Molecular Cell Biology, University College London, WC1E 6BT, London, UK.
authors: Martin
authors: M
authors: Bergert
authors: Medical Research Council Laboratory for Molecular Cell Biology, University College London, WC1E 6BT, London, UK.|Present address: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain.
authors: Kenzo
authors: K
authors: Ivanovitch
authors: Max Planck Institute for the Physics of Complex Systems, Dresden, 01187, Germany.|The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincolns Inn Fields, London, WC2A 3LY, UK.
authors: Guillaume
authors: G
authors: Salbreux
authors: Institute of Science and Technology Austria, Klosterneuburg, 3400, Austria.
authors: Carl-Philipp
authors: CP
authors: Heisenberg
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany.|International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.|Medical Research Council Laboratory for Molecular Cell Biology, University College London, WC1E 6BT, London, UK.
authors: Ewa K
authors: EK
authors: Paluch
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004707:Endoderm / Q000166:cytology; D008648:Mesoderm / Q000166:cytology; D060172:Morpholinos / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D000199:Actins; D060172:Morpholinos
keywords: Actin-rich protrusion; Bleb; Cell migration; Directionality; Persistence; Protrusion orientation; Run and tumble