Broadly our research
is motivated by understanding the link between the mechanics and physiology of
biological materials. Currently our research efforts focus on the cell nucleus.
The cell nucleus is
central to genome integrity, gene expression, and mechanobiology; despite the
major changes that occur in differentiation and disease, the basic physical and
mechanical properties of this important organelle remain poorly understood. We
explore the structure and organization of the nucleus at multiple levels, from
the origins of nuclear shape to subnuclear structure and dynamics, and the
resulting consequences for cellular physiology; to do this we use a
multidisciplinary approach, that includes developing and applying new
technologies to link molecular-scale composition and genotype with biophysical
Our research aims to
link physical properties, structure, and physiological function of the cell
nucleus. We are interested in questions like: What determines the size and
shape of the nucleus? How rigid or squishy are cell nuclei in different cell
and tissue types, and how does this contribute to the deformability of the
whole cell? When the nucleus changes shape, how does that affect the
organization and mobility of components within the nucleus? What are the
implications for physiological function?
To address these
questions, our strategy is to probe cells, tissues, and organisms, merging
techniques from the physical sciences such as micro-fabrication and
-manipulation and quantitative image analysis, with methods in molecular
biology. This includes developing and applying novel high-throughput, single
cell technologies, as well as complementary studies using deformation, higher
resolution imaging, and analysis of individual cells. More broadly, the techniques
we develop can be applied to study the effect of mechanical and chemical
environment on cellular behavior: Why do some cells have a stiffness similar to
Jell-o? How does a cell’s mechanical and physical environment affect its
- Lin Y.C., Broedersz C.P., Rowat A.C., Wedig T., Hermann H., Mackintosh F.C., Weitz D.A., “Divalent cations crosslink vimentin intermediate filament tail domains to regulate network mechanics,” J Mol Biol. 2010 Jun 18;399(4):637-44. Epub 2010 May 4.
- Agresti J.J., Antipov E., Abate A.R., Ahn K., Rowat A.C., Baret J.C., Marquez M., Klibanov A.M., Griffiths A.D., Weitz D.A., “Ultrahigh-throughput screening in drop-based microfluidics for directed evolution,” Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4004-9. Epub 2010 Feb 8. Erratum in: Proc Natl Acad Sci U S A. 2010 Apr6;107(14):6550.
- Rowat A.C., Bird J.C., Agresti J.J., Rando O.J., Weitz D.A., “Tracking lineages of single cells in lines using a microfluidic device,” Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18149-54. Epub 2009 Oct 13.
- Rafat M., Raad D.R., Rowat A.C., Auguste D.T., “Fabrication of reversibly adhesive fluidic devices using magnetism,” Lab Chip. 2009 Oct 21;9(20):3016-9. Epub 2009 Jul 22.
- Schmitz C.H., Rowat A.C., Koster S., Weitz D.A., “Dropspots: a picoliter array in a microfluidic device,” Lab Chip. 2009 Jan 7;9(10:44-9. Epub 2008 Oct 28.
- Ebina W., Rowat A.C., Weitz D.A., “Electrodes on a budget: Micropatterned electrode fabrication by wet chemical deposition,” Biomicrofluidics. 2009 Sep 8;3(3):34104.
- Rowat A.C., “Physical properties of the nucleus studied by micropipette aspiration,” Methods Mol Biol. 2009;464:3-12.
- Koster S., Angile F.E., Duan H., Agresti J.J., Wintner A., Schmitz C., Rowat A.C., Merten C.A., Pisignano D., Griffiths A.D., Weitz D.A., “Drop-based microfluidic devices for encapsulation of single cells,” Lab Chip. 2009 Jul;8(7):1110-5. Epub 2008 May 23.
- Rowat A.C., Lammerding J., Herrmann H., Aebi U., “Towards an integrated understanding of the structure and mechanics of the cell nucleus,” Bioessays. 2008 Mar;30(3):226-36. Review.
- Kasza K.E., Rowat A.C., Liu J., Angelini T.E., Brangwynne C.P., Koenderink G.H., Weitz D.A., “The cell as a material,” Curr Opin Cell Biol. 2007 Feb;19(1):101-7. Epub 2006 Dec 15. Review.