title: Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners.
abstract: Spontaneous molecular oscillations are ubiquitous in biology. But to our knowledge, periodic cell migratory patterns have not been observed. Here we report the highly regular, periodic migration of cells along rectilinear tracks generated inside three-dimensional matrices, with each excursion encompassing several cell lengths, a phenotype that does not occur on conventional substrates. Short hairpin RNA depletion shows that these one-dimensional oscillations are uniquely controlled by zyxin and binding partners α-actinin and p130Cas, but not vasodilator-stimulated phosphoprotein and cysteine-rich protein 1. Oscillations are recapitulated for cells migrating along one-dimensional micropatterns, but not on two-dimensional compliant substrates. These results indicate that although two-dimensional motility can be well described by speed and persistence, three-dimensional motility requires two additional parameters, the dimensionality of the cell paths in the matrix and the temporal control of cell movements along these paths. These results also suggest that the zyxin/α-actinin/p130Cas module may ensure that motile cells in a three-dimensional matrix explore the largest space possible in minimum time.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N Charles Street, Maryland Hall Room 223, Baltimore, Maryland 21218, USA.
authors.forename: Stephanie I
authors.initials: SI
authors.lastname: Fraley
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Feng
authors.forename: Anjil
authors.initials: A
authors.lastname: Giri
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D000185:Actinin / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D060589:Zyxin / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: C493841:BCAR1 protein, human; C486181:CRIP1 protein, human; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D000185:Actinin