Material control of stem cell differentiation: challenges in nano-characterization

• Stem cells are sensitive to and can sometimes remodel extracellular matrix mechanics.
• Nanoscale control of cell-adhesive ligands can direct stem cell behavior.
• ‘The truth is in tissue’ increasingly motivates comparisons to and characterizations of primary tissue.

Recent experiments have revealed that stem cells respond to biophysical cues as well as numerous biochemical factors. Nanoscale properties at the cell–matrix interface that appear to affect adherent stem cells range from matrix elasticity to porosity-dependent matrix tethering and geometry of adhesive linkages. Some stem cells can also remodel their immediate environment to influence phenotype, but this depends on matrix-material properties such as covalent bonding and soft versus hard materials. Efforts to combine both matrix instructions and active cell feedback are required to properly direct stem cell behavior. Comparisons to tissues will be increasingly key and have begun to reveal remodeling of nuclear factors that influence epigenetics.

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