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 the motor protein myosin blocks all elasticity directed lineage specification. While 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, they raise additional questions such as how far cells can feel. This question is addressed with MSCs and a series of gels of controlled thickness, with the results showing that cells probe microns into matrix.