Mechanics and Computation / View source

for Nuclear mechanics and cell phenotype
=Chris Noel Dahl, Ph.D.=

===January 26, 2012===

Nuclear mechanics and cell phenotype

The sequencing of the human genome has provided a wealth of scientific information, but this information is limited by the poor understanding of the mechanisms which control gene expression. We examine changes in nuclear mechanics in cells which are differentiating, de-differentiating via cancer progression and aging. We perform static mechanical measurements of bone marrow derived stem cells, metastatic cancer cells and cells from patients with premature aging. We are able to quantify mechanics and determine contributions of subcellular features, including the nucleus. ‘Undecided’ cells, including stem cells and cancer cells, have much softer nuclei whereas aged cells have stiffer nuclei. We also examine the role that force plays in altering nuclear mechanics and gene expression. Mechanical force and proper cellular response is important during development and for proper homeostatic maintenance of cells and tissues. The genome within the nucleus is a complex, self-assembled structure which has unique mechanical properties capable of responding proportionally to both the magnitude and duration of applied forces. We track subnuclear reorganization in cells with applied forces using particle tracking. We find distinct temporal regimes of subnuclear movements as nuclei adapt to shear stress by stiffening. We have found that native, endogenous structures appear to be in a mechanical homeostasis such that they can sense and adapt optimally to force. Together, it appears that the mechanics and mechanical response of the nuclei in cells is important for proper cell function. 

Kris Noel Dahl:
Associate Professor Carnegie Mellon University
	Department of Biomedical Engineering, Department of Chemical Engineering
Courtesy appointment in Materials Science and Engineering and Department of Biology
Member of CMU-Pitt Molecular Biophysics and Structural Biology, Center for Complex Fluids Engineering, CMU-Pitt Computational Biology, Lance Center for Computational Biology

Associate Director - CMECS
 Center for the Mechanics and Engineering of Cellular Systems

Awards: NSF-CAREER; World Congress of Biomechanics Young Investigator

	Postdoctoral fellowship, Johns Hopkins Medical School in Cell Biology and Anatomy from 2004-2005 funded by NIH-NRSA postdoctoral fellowship; studied nuclear biology and structure
	PhD in Chemical and Biomolecular Engineering from University of Pennsylvania in 2004 funded by a Whitaker graduate fellowship; studied red blood cell mechanics and protein localization
	Worked for Procter and Gamble in Cincinnati for 1 year between MS and PhD
	MS in Chemical Engineering from University of Pennsylvania in 1999; studied non-viral gene therapy
	BS in Chemical Engineering from Carnegie Mellon University in 1998

We study mechanical and rheological properties of the nucleus. In deciphering the structural and mechanical elements of the cell's nucleus we hope to determine roles of epigenetic regulation, stem cell differentiation, aging pathologies and cancer metastases. Mechanical regulation of cell and tissue function is poorly understood but is a fascinating area of study. Our research focuses on molecular, organelle, cellular and multicellular length scales over time, and we use a combination of spectroscopic, imaging, image informatics, biophysics and computational approaches.

http://dahl.cheme.cmu.edu/
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