Research Project

Understanding mechanosensation

Understanding how cells sense and interpret forces, and how this mechanosensation influences various physiological processes.

The sensing of mechanical stresses is fundamental to a wide range of cellular and tissue functions, including hearing, bone remodeling, blood pressure regulation and embryonic and tumor development. Our lab carries out research aimed at understanding how cells sense and interpret these forces, and how this mechanosensation influences various physiological processes. This research is carried out in collaboration with Doug Robinson, of the Department of Cell Biology in the JH School of Medicine.

 

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Myosin II mechanosensation. A. When cells are stressed by applying aspirating pressure with a micropipette, contractile proteins localize to the site of the applied stress. B. To account for this mechanosensation, we developed a model of bipolar thick filament (BTF) assembly of myosin II in the cell cortex. The model considers myosin II monomers, dimers, tetramers and BTFs of different size. It assumes that monomers can be in a number of different configurations and that interconversion between these states is stress-dependent. The reaction scheme leads to reaction-diffusion equations that are solved numerically. C. The model accurately recreates the localization in wild-type cells, as well as the failure for 3xAla myosin II to localize.

Some publications related to this work are:
1.  Luo T, Mohan K, Iglesias PA, Robinson DN. Molecular mechanisms of cellular mechanosensing. Nat Mater. 12:1064-71, 2013.
2. Luo T, Mohan K, Srivastava V, Ren Y, Iglesias PA, Robinson DN. Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensation. Biophys J. 102:238-47, 2012.
3.  Kee YS, Ren Y, Dorfman D, Iijima M, Firtel R, Iglesias PA, Robinson DN. A mechanosensory system governs myosin II accumulation in dividing cells. Mol Biol Cell. 23:1510-23, 2012.
4.  Zhou Q, Kee YS, Poirier CC, Jelinek C, Osborne J, Divi S, Surcel A, Will ME, Eggert US, Müller-Taubenberger A, Iglesias PA, Cotter RJ, Robinson DN.14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis. Curr Biol. 20:1881-9, 2010.
5.  Effler JC, Kee YS, Berk JM, Tran MN, Iglesias PA, Robinson DN. Mitosis-specific mechanosensing and contractile-protein redistribution control cell shape. Curr Biol. 16:1962-7, 2006.

 

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Modular view of the regulatory systems controlling cell shape changes during cytokinesis. Signals, originating at the spindle drive distinct polar/global and equatorial systems which localize different proteins. These affect both the material properties of the system, as well as providing stresses (protrusive at the poles and contractile at the equator.) A mechanosensory system helps to tune the level of contractile proteins allowing the cell to respond to mechanical perturbations

 

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