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PNAS 102 (33): 11594-11599

Copyright © 2005 by the National Academy of Sciences.

From the Cover

APPLIED PHYSICAL SCIENCES / CELL BIOLOGY

Emergent patterns of growth controlled by multicellular form and mechanics

Celeste M. Nelson *, {dagger}, Ronald P. Jean *, John L. Tan *, Wendy F. Liu *, Nathan J. Sniadecki *, Alexander A. Spector *, and Christopher S. Chen *, {dagger}, {ddagger}

*Departments of Biomedical Engineering and Oncology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; and {ddagger}Department of Bioengineering, University of Pennsylvania, Translational Research Labs Suite 1400, 125 South 31st Street, Philadelphia, PA 19104

Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 17, 2005

Received for publication March 29, 2005.

Abstract: Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using microfabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth.

Key Words: morphogenesis • pattern formation • micropatterning • cytoskeleton • mechanotransduction

Author contributions: C.M.N. and C.S.C. designed research; C.M.N., R.P.J., J.L.T., W.F.L., N.J.S., and A.A.S. performed research; C.M.N. and C.S.C. analyzed data; and C.M.N. and C.S.C. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: VE, vascular endothelial; FEM, finite-element method.

See Commentary on page 11571.

{dagger} To whom correspondence may be addressed. E-mail: cmnelson{at}lbl.gov or chrischen{at}seas.upenn.edu.

© 2005 by The National Academy of Sciences of the USA

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