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(Circulation Research. 2008;102:1307.)
© 2008 American Heart Association, Inc.

Reviews

Nuclear Shape, Mechanics, and Mechanotransduction

Kris Noel Dahl, Alexandre J.S. Ribeiro, Jan Lammerding

From the Departments of Biomedical Engineering and Chemical Engineering (N.D., A.J.S.R.), Carnegie Mellon University, Pittsburgh, Pa; and Department of Medicine (J.L.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Kris Noel Dahl, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213. E-mail krisdahl{at}cmu.edu

This Review is part of a thematic series on Nuclear Mechanotransduction, which includes the following articles:

Nuclear Shape, Mechanics, and Mechanotransduction

Emerin and the Nuclear Lamina in Muscle and Cardiac Disease

Mechanical Control of Tissue Morphogenesis
Dennis Discher Guest Editor

In eukaryotic cells, the nucleus contains the genome and is the site of transcriptional regulation. The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell and from force generation within the cell. Here, we discuss the effect of intra- and extracellular forces on nuclear shape and structure and how these force-induced changes could be implicated in nuclear mechanotransduction, ie, force-induced changes in cell signaling and gene transcription. We review mechanical studies of the nucleus and nuclear structural proteins, such as lamins. Dramatic changes in nuclear shape, organization, and stiffness are seen in cells where lamin proteins are mutated or absent, as in genetically engineered mice, RNA interference studies, or human disease. We examine the different mechanical pathways from the force-responsive cytoskeleton to the nucleus. We also highlight studies that link changes in nuclear shape with cell function during developmental, physiological, and pathological modifications. Together, these studies suggest that the nucleus itself may play an important role in the response of the cell to force.

Key Words: nucleus • lamins • gene regulation • force

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