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Matrix elasticity directs stem cell lineage – Better (polymeric) materials for Better biology

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Melville Lecture

Cells make a number of key decisions by actively applying forces to the objects that they ‘touch’. Naive mesenchymal stem cells (MSCs) from human bone marrow will be shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue level elasticity. Soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of myosin blocks all elasticity directed lineage specification – without strongly perturbing many other aspects of cell function and shape. A “Cysteine Shotgun”, Mass Spectrometry-based proteomic method for in situ probing of the ‘foldome’ reveals distinct structural differences attributable to unfolding and/or dissociation of cellular proteins. The results have significant implications for understanding physical effects of the in vivo microenvironment around cells and also for use of materials in biological studies and therapeutic applications of stem cells.

A. Engler, S. Sen, H.L. Sweeney, and D.E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689 (2006). C.P. Johnson, H-Y. Tang, C. Carag, D.W. Speicher, and D.E. Discher. Forced unfolding of proteins within cells. Science 317: 663-666 (2007).

This talk is part of the Melville Laboratory Seminars series.

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