title: Protrusive waves guide 3D cell migration along nanofibers.
abstract: In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Guetta-Terrier
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Pascale
authors.initials: P
authors.lastname: Monzo
authors.affiliation: Cellular and Molecular Physiology, Yale University, New Haven, CT 06520.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore 637459.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Long
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Venkatraman
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cardiovascular Research Institute, National University Health System, Singapore 119228 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: PeiPei
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore 637459 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232.
authors.forename: Sing Yian
authors.initials: SY
authors.lastname: Chew
authors.affiliation: Courant Institute and Department of Biology, New York University, New York, NY 10012.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mogilner
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 Institut Jacques Monod, Centre National de la Recherche Scientifique UMR 7592 and Université Paris Diderot, 75013 Paris, France benoit.ladoux@ijm.fr nils.gauthier@gmail.com.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 benoit.ladoux@ijm.fr nils.gauthier@gmail.com.
authors.forename: Nils C
authors.initials: NC
authors.lastname: Gauthier
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D041681:NIH 3T3 Cells; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D005353:Fibronectins; D000205:Actomyosin