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Matrix Elasticity Directs StemCell Lineage Specification

stem cell

stemcell

Matrix Elasticity Directs StemCell Lineage Specification


Adam J. Engler,1,2Shamik Sen,1,2H. Lee Sweeney,1and Dennis E. Discher1,2,3,4,

1 Pennsylvania Muscle Institute

2 School of Engineering and Applied Science

3 Cell & Molecular Biology Graduate Group

4 Physics Graduate

GroupUniversity of Pennsylvania, Philadelphia, PA 19104, USA

*Contact:discher@seas.upenn.eduDOI 10.1016/j.cell.2006.06.044


:SUMMARYM


icroenvironments appear important in stem cell lineage specification but can be difficult toadequately characterize or control with soft tis-sues. Naive mesenchymal stem cells (MSCs)are shown here to specify lineage and commit tophenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brainare neurogenic, stiffer matrices that mimic mus-cle are myogenic, and comparatively rigidmatrices that mimic collagenous bone proveosteogenic. During the initial week in culture,reprogramming of these lineages is possiblewith addition of soluble induction factors, butafter several weeks in culture, the cells committo the lineage specified by matrix elasticity,consistent with the elasticity-insensitive com-mitment of differentiated cell types. Inhibitionof nonmuscle myosin II blocks all elasticity-directed lineage specification–without stronglyperturbing many other aspects of cell functionand shape. The results have significant implica-tions for understanding physical effects of thein vivo microenvironment and also for therapeu-tic uses of stem cells


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