title: Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration.
abstract: Fast amoeboid migration requires cells to apply mechanical forces on their surroundings via transient adhesions. However, the role these forces play in controlling cell migration speed remains largely unknown. We used three-dimensional force microscopy to measure the three-dimensional forces exerted by chemotaxing Dictyostelium cells, and examined wild-type cells as well as mutants with defects in contractility, internal F-actin crosslinking, and cortical integrity. We showed that cells pull on their substrate adhesions using two distinct, yet interconnected mechanisms: axial actomyosin contractility and cortical tension. We found that the migration speed increases when axial contractility overcomes cortical tension to produce the cell shape changes needed for locomotion. We demonstrated that the three-dimensional pulling forces generated by both mechanisms are internally balanced by an increase in cytoplasmic pressure that allows cells to push on their substrate without adhering to it, and which may be relevant for amoeboid migration in complex three-dimensional environments.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California; Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, San Diego, California.
authors.forename: Begoña
authors.initials: B
authors.lastname: Álvarez-González
authors.affiliation: Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, San Diego, California.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Meili
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California; Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, San Diego, California.
authors.forename: Effie
authors.initials: E
authors.lastname: Bastounis
authors.affiliation: Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, San Diego, California.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Firtel
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California; Department of Bioengineering, University of California at San Diego, San Diego, California; Institute for Engineering in Medicine, University of California at San Diego, San Diego, California.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Lasheras
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California; Institute for Engineering in Medicine, University of California at San Diego, San Diego, California. Electronic address: jalamo@ucsd.edu.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Del Álamo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism*; D002633:Chemotaxis; D003593:Cytoplasm / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism* / Q000502:physiology
chemical_list: D000199:Actins; D000205:Actomyosin