title: Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces.
abstract: Directed cell migration is critical for tissue morphogenesis and wound healing, but the mechanism of directional control is poorly understood. Here we show that the direction in which cells extend their leading edge can be controlled by constraining cell shape using micrometer-sized extracellular matrix (ECM) islands. When cultured on square ECM islands in the presence of motility factors, cells preferentially extended lamellipodia, filopodia, and microspikes from their corners. Square cells reoriented their stress fibers and focal adhesions so that tractional forces were concentrated in these corner regions. When cell tension was dissipated, lamellipodia extension ceased. Mechanical interactions between cells and ECM that modulate cytoskeletal tension may therefore play a key role in the control of directional cell motility.
authors.affiliation: Department of Pathology and Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
authors.forename: Amy Lepre
authors.initials: AL
authors.lastname: Brock
authors.forename: Cliff
authors.initials: C
authors.lastname: Brangwynne
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mannix
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Emanuele
authors.initials: E
authors.lastname: Ostuni
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Geisse
authors.forename: Josephine C
authors.initials: JC
authors.lastname: Adams
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002465:Cell Movement; D048429:Cell Size; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D022001:Focal Adhesions / Q000648:ultrastructure; D051379:Mice; D011554:Pseudopodia / Q000648:ultrastructure*; D022502:Stress Fibers / Q000648:ultrastructure; D013314:Stress, Mechanical
keywords: NASA Discipline Cell Biology; NASA Program Fundamental Space Biology; Non-NASA Center