Translating Biomaterial Properties to Intracellular Signaling

Bioactive materials present important micro-environmental cues that induce specific intracellular signaling responses which ultimately determine cell behavior. For example, vascular endothelial cells on a normal vessel wall resist inflammation and thrombosis, but the same cells seeded on an artificial vascular graft or stent do not. What makes these cells behave so differently when they are adhered to different materials? Intracellular signaling from integrins and other cell-surface receptors is an important part of the answer, but these signaling responses constitute a highly-branched, interconnected network of molecules. In order to perform rational design of biomaterials, one must understand how altering the properties of the material (micro-environment) causes changes in cell behavior, and this in turn requires understanding the complex signaling response. Systems biology and mathematical modeling aid analysis of the connectivity of this network. This review summarizes applicable systems biology and mathematical modeling techniques including ordinary differential equations-based models, principal component analysis, and Bayesian networks. Next covered is biomaterials research which studies the intracellular signaling responses generated by variation of biomaterial properties. Finally, the review details ways in which modeling has been or could be applied to better understand the link between biomaterial properties and intracellular signaling.