Molecular Mechanisms Controlling Cell Shape

Maintenance of cell shape is central to many aspects of biology such as organism growth and form. One ubiquitous example of cell shape change occurs during mitosis, where animal cells round up to divide in tissue layers in vivo. Mitotic rounding plays a role in tissue development, maintaining tissue organization and is involved in epidermis differentiation, tracheal invagination and maintenance of pseudostratified epithelia. Counteracting mitotic rounding by confinement results in prolonged or defective mitosis due to failure of the mitotic spindle to properly capture and organize chromosomes. Furthermore, spindle orientation, another key aspect of mitotic geometry, is controlled by the arrangement of retraction fibres extruded from substrate adhesions during rounding. Thus, the mechanisms rounding animal cells play important biological roles in multiple aspects of mitosis. In this research project we mainly characterize these fundamental mechanisms and could find basic mechanisms how mitotic cells prepare for the rounding and regulate rounding. However, in some cases we also characterize mechanisms guiding cell shape in cell states other than mitosis.

Investigating mitosis of a single cancer cell by Atomic Force Spectroscopy (for more information see M. Stewart et al. Nature (2011) 469, 226-230)
Investigating mitosis of a single cancer cell by Atomic Force Spectroscopy (for more information see M. Stewart et al. Nature (2011) 469, 226-230)

Publications on the topic

Rheology of the active cell cortex in mitosis

E. Fischer-Friedrich, Y. Toyoda, C.J. Cattin, D.J. Müller, A.A. Hyman & F. Jülicher 
Biophysical Journal
(2016) 111, 589-600.

A glucose-starvation response regulates the diffusion of macromolecules

R.P. Joyner, J.H. Tang, J. Helenius, E. Dultz, C. Brune, L.J. Holt, S. Huet, D.J. Müller & K. Weis
eLife
(2016) 5, e09376.

Mitotic cells contract actomyosin cortex and generate pressure to round up against or escape epithelial confinement

B. Sorce, C. Escobedo, Y. Toyoda, M.P. StewartC.J. CattinR. Newton, I. Banerjee, A. Stettler, B. Roska, S. Eaton, A.A. Hyman, A. Hierlemann & D.J. Müller 
Nature Communications (2015) 6, 8872. external pageonline

Mechanical control of mitotic progression in single animal cells

C.J. Cattin, M. Düggelin, D. Martinez-Martin, C. Gerber, D.J. Müller & M.P. Stewart
Proc. Natl. Acad. Sci. USA (2015), 112, 11258-112.

Cdk1 dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement

S.P. RamanathanJ. Helenius, C. Cattin, M.P. Stewart, A.A. Hyman & D.J. Muller
Nature Cell Biology (2015) 17, 148-159.

Products of the Parkinson's-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

Y. Toyoda, C. Erkut, F. Pan-Montojo, S. Boland, M.P. StewartD.J. Müller, W. Wurst, A.A. Hyman & T.V. Kurzchalia
Biology Open (2014) 3, 777-784.

Quantification of surface tension and internal pressure generated by single mitotic cells

E. Fischer-Friedrich, A.A. Hyman, F. Jülicher, D.J. Muller & J. Helenius
Scientific Reports (2014) 4, 6213.

Wedged AFM-cantilevers for parallel plate cell mechanics

M.P. Stewart, A.W. Hodel, A. Spielhofer, C.J. Cattin, D.J. Müller & J. Helenius
Methods (2013) 60, 186–194.

Tracking mechanics and volume of globular cells with atomic force microscopy using constant height clamp

M.P. Stewart, Y. Toyoda, A.A. Hyman & D.J. Muller
Nature Protocols (2012) 7, 143-154.

Force probing cell shape changes to molecular resolution

M.P. Stewart, Y. Toyoda, A.A. Hyman & D.J. Muller
Trends in Biochemical Sciences (2011) 36, 444-450.

Combined activities of hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding

M.P. Stewart, J. Helenius, Y. Toyoda, S.P. RamanathanD.J. Müller & A.A. Hyman
Nature (2011) 469, 226–230.

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