Polysaccharide hydrogels with tunable stiffness and provasculogenic properties via  a-helix to b-sheet switch in secondary structure.

August 2013

Forget, A.; Christensen, J.; Lüdeke, S.; Kohler, E.; Tobias, S.; Matloubi, M.; Thomann, R. and Shastri, V. P.

Proc. Natl. Acad. Sci. 2013, i, 1–6

Mechanical aspects of the cellular environment can influence cell function, and in this context hydrogels can serve as an instructive matrix. Here we report that physicochemical properties of hydrogels derived from polysaccharides (agarose, κ-carrageenan) having an α-helical backbone can be tailored by inducing a switch in the secondary structure from α-helix to β-sheet through carboxylation. This enables the gel modulus to be tuned over four orders of magnitude (G′ 6 Pa–3.6 × 104 Pa) independently of polymer concentration and molecular weight. Using carboxylated agarose gels as a screening platform, we demonstrate that soft-carboxylated agarose provides a unique environment for the polarization of endothelial cells in the presence of soluble and bound signals, which notably does not occur in fibrin and collagen gels. Furthermore, endothelial cells organize into freestanding lumens over 100 μm in length. The finding that a biomaterial can modulate soluble and bound signals provides impetus for exploring mechanobiology paradigms in regenerative therapies.