title: Temporal differences in Erk1/2 activity distinguish among combinations of extracellular matrix components.
abstract: Rational design of biomaterials requires understanding how cells interrogate their microenvironment. In this study, human umbilical vein endothelial cells are cultured on combinations of extracellular matrix (ECM) components (collagen I, collagen IV, vitronectin, fibronectin, laminin, heparan sulfate proteoglycan, chondroitin sulfate proteoglycan), and the phosphorylation of four intracellular signaling kinases (Erk1/2, JNK, Akt1, and NFκB) is quantified. These combinations of ECM components elicit different temporal patterns of Erk1/2 phosphorylation. Collagen I-containing substrates cause Erk1/2 phosphorylation to reach maximal levels at 30 min and remain near maximal levels until 90 min. Collagen IV/laminin substrates elicit maximal phosphorylation at 30-45 min, and then phosphorylation decreases substantially at 60-90 min. All other combinations studied (collagen IV and vitronectin-based combinations) cause an increase in phosphorylation at 30-45 min, but not to maximal levels; maximal phosphorylation is reached by 60-90 min. These temporal patterns of phosphorylation may explain how a limited number of intracellular signaling pathways can distinguish among thousands of possible combinations of microenvironmental cues by adding to the information contained in each cell signaling pathway.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Pauken
authors.forename: Michael R
authors.initials: MR
authors.lastname: Caplan
mesh_terms: D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3