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Abstract
Microenvironments appear important in stem cell lineage specification but can be difficult
to adequately characterize or control with soft tissues. Naive mesenchymal stem cells
(MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity
to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer
matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic
collagenous bone prove osteogenic. During the initial week in culture, reprogramming
of these lineages is possible with addition of soluble induction factors, but after
several weeks in culture, the cells commit to the lineage specified by matrix elasticity,
consistent with the elasticity-insensitive commitment of differentiated cell types.
Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without
strongly perturbing many other aspects of cell function and shape. The results have
significant implications for understanding physical effects of the in vivo microenvironment
and also for therapeutic uses of stem cells.