Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces.
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.
Parker
Kevin Kit
KK
Department of Pathology and Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Brock
Amy Lepre
AL
Brangwynne
Cliff
C
Mannix
Robert J
RJ
Wang
Ning
N
Ostuni
Emanuele
E
Geisse
Nicholas A
NA
Adams
Josephine C
JC
Whitesides
George M
GM
Ingber
Donald E
DE
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
NASA Discipline Cell Biology; NASA Program Fundamental Space Biology; Non-NASA Center