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. Author manuscript; available in PMC: 2018 Jun 1.

Published in final edited form as: Nat Rev Mol Cell Biol. 2017 Nov 8;18(12):728–742. doi: 10.1038/nrm.2017.108

Material systems to study stem cell mechanobiology. When engineering a synthetic niche, alterations in the overall polymer concentration may change the density of adhesion ligands, while changing crosslinking without altering the polymer content may vary the network mesh size (spacing between crosslinks), which can affect how molecules diffuse through the network. A) Artificial niches fabricated from naturally-derived ECM typically manipulate stiffness by altering the concentration of the matrix proteins, which increases ligand density and decreases mesh size in parallel. B) Synthetic polymer systems can offer independent control of stiffness and ligand density, by maintaining a constant polymer concentration while altering the crosslink density. However, the mesh size is altered in parallel. C) Matrices formed from alginate polymers can be crosslinked to various extents while maintaining constant ligand density and mesh size, and thus enable one to independently examine how matrix stiffness affects stem cells. (Inset) Crosslinking in this system occurs via cooperative sharing of divalent cations (red) in blocks of one type of sugar residue (G-block) on the chains, and increases in the number of crosslink sites occupied in the aligned blocks do not alter the architecture of the chains. D) Alginate polymer molecular weight (MW) can be used to control the viscoelasticity of an ionically-crosslinked alginate network. Low MW alginate (red arrow and box) forms into a network with less physical entanglement and overlap of the alginate chains. High MW alginate (purple arrow and box) has higher chain entanglement and overlap (shaded blue region), which decreases the ability of the polymer network dissipate stress. E) The low MW network (red line) is more viscous, shown by its rapid relaxation of stress while a constant strain is applied. The high MW network (purple line) dissipates stress more slowly due to more physical entanglement and overlap. The covalently-crosslinked network (black line) is more elastic than the viscoelastic reversibly-crosslinked alginate, and does not significantly dissipate stress over time.

Material systems to study stem cell mechanobiology. When engineering a synthetic niche, alterations in the overall polymer concentration may change the density of adhesion ligands, while changing crosslinking without altering the polymer content may vary the network mesh size (spacing between crosslinks), which can affect how molecules diffuse through the network. A) Artificial niches fabricated from naturally-derived ECM typically manipulate stiffness by altering the concentration of the matrix proteins, which increases ligand density and decreases mesh size in parallel. B) Synthetic polymer systems can offer independent control of stiffness and ligand density, by maintaining a constant polymer concentration while altering the crosslink density. However, the mesh size is altered in parallel. C) Matrices formed from alginate polymers can be crosslinked to various extents while maintaining constant ligand density and mesh size, and thus enable one to independently examine how matrix stiffness affects stem cells. (Inset) Crosslinking in this system occurs via cooperative sharing of divalent cations (red) in blocks of one type of sugar residue (G-block) on the chains, and increases in the number of crosslink sites occupied in the aligned blocks do not alter the architecture of the chains. D) Alginate polymer molecular weight (MW) can be used to control the viscoelasticity of an ionically-crosslinked alginate network. Low MW alginate (red arrow and box) forms into a network with less physical entanglement and overlap of the alginate chains. High MW alginate (purple arrow and box) has higher chain entanglement and overlap (shaded blue region), which decreases the ability of the polymer network dissipate stress. E) The low MW network (red line) is more viscous, shown by its rapid relaxation of stress while a constant strain is applied. The high MW network (purple line) dissipates stress more slowly due to more physical entanglement and overlap. The covalently-crosslinked network (black line) is more elastic than the viscoelastic reversibly-crosslinked alginate, and does not significantly dissipate stress over time.