spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online April 24, 2006
doi: 10.1242/10.1242/jcs.02899

Journal of Cell Science 119, 1760-1768 (2006)
Published by The Company of Biologists 2006
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, J. S. H.
Right arrow Articles by Wirtz, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J. S. H.
Right arrow Articles by Wirtz, D.

Research Article

Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow

Jerry S. H. Lee1,*, Porntula Panorchan1, Christopher M. Hale1, Shyam B. Khatau1, Thomas P. Kole1, Yiider Tseng1,2 and Denis Wirtz1,3,*

1 Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA
2 Department of Chemical Engineering, University of Florida, Gainsville, FL 32011, USA
3 Howard Hughes Medical Institute graduate training program, The Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA

* Authors for correspondence (e-mail: wirtz{at}jhu.edu; jslee{at}jhu.edu)

Accepted 19 January 2006

Cells in vivo are constantly subjected to mechanical shear stresses that play important regulatory roles in various physiological and pathological processes. Cytoskeletal reorganizations that occur in response to shear flow have been studied extensively, but whether the cytoplasm of an adherent cell adapts its mechanical properties to respond to shear is largely unknown. Here we develop a new method where fluorescent nanoparticles are ballistically injected into the cells to probe, with high resolution, possible local viscoelastic changes in the cytoplasm of individual cells subjected to fluid flow. This new assay, ballistic intracellular nanorheology (BIN), reveals that shear flow induces a dramatic sustained 25-fold increase in cytoplasmic viscosity in serum-starved Swiss 3T3 fibroblasts. By contrast, cells stimulated with the actin contractile agonist LPA show highly transient stiffening of much lower amplitude, despite the formation of similar cytoskeletal structures. Shear-induced cytoplasmic stiffening is attenuated by inhibiting actomyosin interactions and is entirely eliminated by specific Rho-kinase (ROCK) inhibition. Together, these results show that biochemical and biophysical stimuli may elicit the formation of qualitatively similar cytoskeleton structures (i.e. stress fibers and focal adhesions), but induces quantitatively different micromechanical responses. Our results suggest that when an adherent cell is subjected to shear stresses, its first order of action is to prevent detachment from its substratum by greatly stiffening its cytoplasm through enhanced actin assembly and Rho-kinase mediated contractility.

Key words: Cell mechanics, Rho GTPases, Fluid shear stress, Actin, Microtubule




This article has been cited by other articles:


Home page
 Biophys. JHome page
C. M. Hale, A. L. Shrestha, S. B. Khatau, P. J. Stewart-Hutchinson, L. Hernandez, C. L. Stewart, D. Hodzic, and D. Wirtz
Dysfunctional Connections Between the Nucleus and the Actin and Microtubule Networks in Laminopathic Models
Biophys. J., December 1, 2008; 95(11): 5462 - 5475.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. C. del Alamo, G. N. Norwich, Y.-s. J. Li, J. C. Lasheras, and S. Chien
Anisotropic rheology and directional mechanotransduction in vascular endothelial cells
PNAS, October 7, 2008; 105(40): 15411 - 15416.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
W. M. Jackson, M. J. Jaasma, R. Y. Tang, and T. M. Keaveny
Mechanical loading by fluid shear is sufficient to alter the cytoskeletal composition of osteoblastic cells
Am J Physiol Cell Physiol, October 1, 2008; 295(4): C1007 - C1015.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
X. Zhou, R. G. Rowe, N. Hiraoka, J. P. George, D. Wirtz, D. F. Mosher, I. Virtanen, M. A. Chernousov, and S. J. Weiss
Fibronectin fibrillogenesis regulates three-dimensional neovessel formation
Genes & Dev., May 1, 2008; 22(9): 1231 - 1243.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
D. Icard-Arcizet, O. Cardoso, A. Richert, and S. Henon
Cell Stiffening in Response to External Stress is Correlated to Actin Recruitment
Biophys. J., April 1, 2008; 94(7): 2906 - 2913.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. H. Dangaria and P. J. Butler
Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress
Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1568 - C1575.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
J. S. H. Lee, C. M. Hale, P. Panorchan, S. B. Khatau, J. P. George, Y. Tseng, C. L. Stewart, D. Hodzic, and D. Wirtz
Nuclear Lamin A/C Deficiency Induces Defects in Cell Mechanics, Polarization, and Migration
Biophys. J., October 1, 2007; 93(7): 2542 - 2552.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
P. Panorchan, J. S. H. Lee, T. P. Kole, Y. Tseng, and D. Wirtz
Microrheology and ROCK Signaling of Human Endothelial Cells Embedded in a 3D Matrix
Biophys. J., November 1, 2006; 91(9): 3499 - 3507.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006