| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Pathology and Surgery, Children’s Hospital, Harvard Medical School;
* Physiology Program, Harvard School of Public Health, Boston, Massachusetts, USA;
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA;
Department of Physics, Boston University, Boston, Massachusetts, USA; and
MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, London, UK
1Correspondence: Departments of Surgery and Pathology, Children’s Hospital-Harvard Medical School, Enders 1007, 300 Longwood Ave., Boston, MA 02115, USA. E-mail: donald.ingber{at}tch.harvard.edu
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, K. K., Brock, A. L., Brangwynne, C., Mannix, R. J., Wang, N., Ostuni, E., Geisse, N. A., Adams, J. C., Whitesides, G. M., Ingber, D. E. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces.
Key Words: migration • motility • focal adhesion • cell tension • microspike • microcontact printing
This article has been cited by other articles:
|
|
 |
|
  K. R. Chien, I. J. Domian, and K. K. Parker Cardiogenesis and the Complex Biology of Regenerative Cardiovascular Medicine Science, December 5, 2008; 322(5907): 1494 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Parker, J. Tan, C. S. Chen, and L. Tung Myofibrillar Architecture in Engineered Cardiac Myocytes Circ. Res., August 15, 2008; 103(4): 340 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Pouthas, P. Girard, V. Lecaudey, T. B. N. Ly, D. Gilmour, C. Boulin, R. Pepperkok, and E. G. Reynaud In migrating cells, the Golgi complex and the position of the centrosome depend on geometrical constraints of the substratum J. Cell Sci., July 15, 2008; 121(14): 2406 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pathak, V. S Deshpande, R. M McMeeking, and A. G Evans The simulation of stress fibre and focal adhesion development in cells on patterned substrates J R Soc Interface, May 6, 2008; 5(22): 507 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-h. Guo and Y.-l. Wang Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals Mol. Biol. Cell, November 1, 2007; 18(11): 4519 - 4527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hashimoto, M. Parsons, and J. C. Adams Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to Metastasis Mol. Biol. Cell, November 1, 2007; 18(11): 4591 - 4602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K Parker and D. E Ingber Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering Phil Trans R Soc B, August 29, 2007; 362(1484): 1267 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Arciniegas, M. G. Frid, I. S. Douglas, and K. R. Stenmark Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L1 - L8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S Deshpande, R. M McMeeking, and A. G Evans A model for the contractility of the cytoskeleton including the effects of stress-fibre formation and dissociation Proc R Soc A, March 8, 2007; 463(2079): 787 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mammoto, S. Huang, and D. E. Ingber Filamin links cell shape and cytoskeletal structure to Rho regulation by controlling accumulation of p190RhoGAP in lipid rafts J. Cell Sci., February 1, 2007; 120(3): 456 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Deshpande, R. M. McMeeking, and A. G. Evans A bio-chemo-mechanical model for cell contractility PNAS, September 19, 2006; 103(38): 14015 - 14020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Brangwynne, F. C. MacKintosh, S. Kumar, N. A. Geisse, J. Talbot, L. Mahadevan, K. K. Parker, D. E. Ingber, and D. A. Weitz Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement J. Cell Biol., June 5, 2006; 173(5): 733 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Matthews, D. R. Overby, R. Mannix, and D. E. Ingber Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels J. Cell Sci., February 1, 2006; 119(3): 508 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. An, C. M. Pennella, A. Gonnabathula, J. Chen, N. Wang, M. Gaestel, P. M. Hassoun, J. J. Fredberg, and U. S. Kayyali Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways Am J Physiol Cell Physiol, September 1, 2005; 289(3): C521 - C530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides Directing cell migration with asymmetric micropatterns PNAS, January 25, 2005; 102(4): 975 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, J. L. C. Lin, R. S. Reiter, K. Daniels, D. R. Soll, and J. J. C. Lin Caldesmon mutant defective in Ca2+-calmodulin binding interferes with assembly of stress fibers and affects cell morphology, growth and motility J. Cell Sci., July 15, 2004; 117(16): 3593 - 3604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mammoto, S. Huang, K. Moore, P. Oh, and D. E. Ingber Role of RhoA, mDia, and ROCK in Cell Shape-dependent Control of the Skp2-p27kip1 Pathway and the G1/S Transition J. Biol. Chem., June 18, 2004; 279(25): 26323 - 26330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. An, B. Fabry, M. Mellema, P. Bursac, W. T. Gerthoffer, U. S. Kayyali, M. Gaestel, S. A. Shore, and J. J. Fredberg Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell J Appl Physiol, May 1, 2004; 96(5): 1701 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Carman, C.-D. Jun, A. Salas, and T. A. Springer Endothelial Cells Proactively Form Microvilli-Like Membrane Projections upon Intercellular Adhesion Molecule 1 Engagement of Leukocyte LFA-1 J. Immunol., December 1, 2003; 171(11): 6135 - 6144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Ingber Tensegrity II. How structural networks influence cellular information processing networks J. Cell Sci., April 15, 2003; 116(8): 1397 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Ingber Mechanosensation through integrins: Cells act locally but think globally PNAS, February 18, 2003; 100(4): 1472 - 1474. [Full Text] [PDF]
|
|
|
|
|
|
N. Bursac, K.K. Parker, S. Iravanian, and L. Tung Cardiomyocyte Cultures With Controlled Macroscopic Anisotropy: A Model for Functional Electrophysiological Studies of Cardiac Muscle Circ. Res., December 13, 2002; 91 (12): e45 - e54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Ingber Mechanical Signaling and the Cellular Response to Extracellular Matrix in Angiogenesis and Cardiovascular Physiology Circ. Res., November 15, 2002; 91(10): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
