Figure 4.

Fibronectin (FN) nanonetwork formation and growth factor (GF) presentation. (a) FN has three types of domains involved in FN–FN interactions (I_1–5), GF sequestration (III_12–14) and integrin binding (III_9–10). (b) Atomic force microscopy (AFM) images after FN adsorption shows spontaneous formation of FN nanonetworks on PEA, but not PMA which results in globular FN aggregates. Sequential adsorption of growth factor (here BMP-2, at 25 ng ml⁻¹) shows interactions of BMP-2 with FN fibrils on PEA, but not PMA, due to an open molecular conformation exposing the key GF binding domain. The proximity of the GF binding and integrin binding domain on FN molecules in networks leads to synergistic integrin and GF receptor signalling. (c) Conventional solubilized GF delivery (right) normally requires high dosages, making it less efficient than ECM-bound (or solid-phase presenting) systems (left) that may use several orders of magnitude lower dosages, allowing efficient, targeted delivery that also has the potential to facilitate cross-talk between integrins and growth factor receptors. (a) Adapted from and (b) taken from reference [130]. © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution License 4.0 (CC BY). (c) Adapted from reference [65]. (Online version in colour.)