title: Adaptive force transmission in amoeboid cell migration.
abstract: The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane. Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family. Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue.
authors.affiliation: Max Planck Institute of Biochemistry, Hofschneider Group Leukocyte Migration, 82152 Martinsried, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Renkawitz
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schumann
authors.forename: Michele
authors.initials: M
authors.lastname: Weber
authors.forename: Tim
authors.initials: T
authors.lastname: Lämmermann
authors.forename: Holger
authors.initials: H
authors.lastname: Pflicke
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
authors.forename: Julien
authors.initials: J
authors.lastname: Polleux
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Spatz
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
mesh_terms: D000199:Actins / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D013379:Substrate Specificity
chemical_list: D000199:Actins; D054415:Chemokine CCL19; D016023:Integrins