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Mathematical modeling and systems biology approach to study biomaterial composition‐mediated inflammatory signals in endothelial cells

Understanding of intracellular signaling in response to biomaterials is crucial for rational design of bioactive materials that elicit desired cellular behavior. To understand correlation of signaling to recruitment of inflammation by endothelial cells, human umbilical vein endothelial cells (HUVECs) were cultured on substrates prepared by adsorbing nine different extracellular matrix components to tissue culture plates in addition to a non‐adsorbed plate. Activation of kinases (ERK1/2, JNK‐1, Akt and IKK) was quantified by high‐throughput kinase assays for HUVECs exposed to these surfaces for various times. Principal component analysis (PCA), a well‐known matrix analysis technique, indicates that principal component 1 (PC1), captured the most information, is positively correlated to JNK activity, gelatin, polystyrene and negatively to chondroitin sulfate. PC2 correlated positively to ERK1/2 activity, vitronectin and negatively to Akt activity, chondroitin sulfate and heparin sulfate. PC3 correlated mostly with IKK activity, and PC3 is high for matrigel and laminin but low for vitronectin and heparan sulfate. Correlating these observations with ICAM‐1/E‐selectin expression and leukocyte adhesion will provide further insight into biomaterial composition‐mediated inflammatory signals in endothelial cells.