Journal
PLOS ONE
Volume 6, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0015978
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Funding
- National Institutes of Health [1DP02OD006460]
- American Heart Association [0865150F]
- National Science Foundation [0754718]
- Div Of Engineering Education and Centers
- Directorate For Engineering [0754718] Funding Source: National Science Foundation
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Mesenchymal stem cell (MSC) differentiation is regulated in part by tissue stiffness, yet MSCs can often encounter stiffness gradients within tissues caused by pathological, e.g., myocardial infarction similar to 8.7 +/- 1.5 kPa/mm, or normal tissue variation, e.g., myocardium similar to 0.6 +/- 0.9 kPa/mm; since migration predominantly occurs through physiological rather than pathological gradients, it is not clear whether MSC differentiate or migrate first. MSCs cultured up to 21 days on a hydrogel containing a physiological gradient of 1.0 +/- 0.1 kPa/mm undergo directed migration, or durotaxis, up stiffness gradients rather than remain stationary. Temporal assessment of morphology and differentiation markers indicates that MSCs migrate to stiffer matrix and then differentiate into a more contractile myogenic phenotype. In those cells migrating from soft to stiff regions however, phenotype is not completely determined by the stiff hydrogel as some cells retain expression of a neural marker. These data may indicate that stiffness variation, not just stiffness alone, can be an important regulator of MSC behavior.
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