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Blood, 13 August 2009, Vol. 114, No. 7, pp. 1387-1395. Prepublished online as a Blood First Edition Paper on June 2, 2009; DOI 10.1182/blood-2008-11-191445. This Article Full Text Full Text (PDF) Supplemental Methods, Table, Figure, and Videos All Versions of this Article: blood-2008-11-191445v1 114/7/1387    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Oakes, P. W. Articles by Tang, J. X. PubMed PubMed Citation Articles by Oakes, P. W. Articles by Tang, J. X. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Neutrophil morphology and migration are affected by substrate elasticity Patrick W. Oakes1, Dipan C. Patel2, Nicole A. Morin2, Daniel P. Zitterbart3, Ben Fabry3, Jonathan S. Reichner2, and Jay X. Tang1 1 Department of Physics, Brown University, Providence, RI; 2 Department of Surgery, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence; and 3 Center for Medical Physics and Technology, Biophysics Group, University of Erlangen-Nuremberg, Erlangen, Germany To reach sites of inflammation, neutrophils execute a series of adhesion and migration events that include transmigration through the vascular endothelium and chemotaxis through the vicinal extracellular matrix until contact is made with the point of injury or infection. These in vivo microenvironments differ in their mechanical properties. Using polyacrylamide gels of physiologically relevant elasticity in the range of 5 to 100 kPa and coated with fibronectin, we tested how neutrophil adhesion, spreading, and migration were affected by substrate stiffness. Neutrophils on the softest gels showed only small changes in spread area, whereas on the stiffest gels they showed a 3-fold increase. During adhesion and migration, the magnitudes of the distortions induced in the gel substrate were independent of substrate stiffness, corresponding to the generation of significantly larger traction stresses on the stiffer gels. Cells migrated more slowly but more persistently on stiffer substrates, which resulted in neutrophils moving greater distances over time despite their slower speeds. The largest tractions were localized to the posterior of migrating neutrophils and were independent of substrate stiffness. Finally, the phosphatidylinositol 3-kinase inhibitor LY294002 obviated the ability to sense substrate stiffness, suggesting that phosphatidylinositol 3-kinase plays a mechanistic role in neutrophil mechanosensing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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