Cells as smart materials: Quantitatively dissecting and rebuilding mechanibiological units

Date

Oct 24, 2014

Time

11:00 AM - 12:00 PM

Speaker

Prof. Sanjay Kumar, University of California, Berkeley Department of Bioenineering

Language

en

Main Topic

Biologie

Other Topics

Biologie, Medizin

Host

Jochen Guck

Description

Please contact the host ( ) if you would like to talk to the speaker. Everybody is welcome! ------------------------------------------------------------------------ Abstract: Living cells are capable of processing a variety of mechanical signals encoded within their microenvironment, which can in turn act through the cellular structural machinery to regulate many fundamental behaviors. In this sense, cells may be regarded as smart materials” that dynamically and locally modulate their physical properties in response to environmental stimuli. Here we discuss our recent efforts to dissect, control, and mimic these phenomena. First, we have used laser nanosurgery to spatially map the nanomechanical properties of actomyosin stress fibers. We have combined this approach with advanced molecular imaging tools (FRAP, FRET) to relate intracellular tensile forces to the conformational activation of mechanosensory proteins at the cell-microenvironment interface and the activities of specific myosin activators and isoforms. Second, we have used the tools of synthetic biology to precisely control the expression and activation of mechanoregulatory proteins in single cells using multiple mutually orthogonal inducer/repressor systems. This capability has enabled us to quantitatively elucidate relationships between signal activation and phenotype and to deconstruct complex signaling networks. By combining these genetic approaches with advanced culture paradigms and in vivo models, we have been able to explore how mechanobiological signals may help drive stem cell differentiation and tumor invasion in the central nervous system. We are now beginning to close the loop by engineering proteins that mimic the stimulus-responsive features of cellular structural networks and may serve as smart, genetically-encoded mechanochemical building blocks. Publications: A. J. Keung*, E. M. de Juan-Pardo*, D. V. Schaffer, and S. Kumar (2011). Rho GTPases Mediate the Mechanosensitive Lineage Commitment of Neural Stem Cells.” Stem Cells 29: 1886-1897 [*equal contribution]. A. Pathak and S. Kumar (2012). Independent regulation of tumor cell migration by matrix stiffness and confinement. Proceedings of the National Academy of Sciences (PNAS) 109: 10334-10339. C.-W. Chang and S. Kumar (2013). Vinculin tension distributions of individual stress fibers within cell-matrix adhesions. Journal of Cell Science 126: 3021-3030. Y. Kim and S. Kumar (2014). CD44-mediated adhesion to hyaluronic acid contributes to mechanosensing and invasive motility. Molecular Cancer Research (DOI 10.1158/1541-7786.MCR-13-0629). N. Srinivasan, M. Bhagawati, B. Ananthanarayanan, and S. Kumar (2014). Stimuli-sensitive intrinsically disordered protein brushes. Nature Communications 5: 5145.

Links

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Last modified: Oct 24, 2014, 12:56:56 PM