Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.

Original publication

DOI

10.1073/pnas.1419799112

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

07/04/2015

Volume

112

Pages

4280 - 4285

Keywords

human mesenchymal stem cells, mevalonate pathway, microarray analysis, sparse feature selection analysis, strontium-releasing biomaterials, Biocompatible Materials, Bone Regeneration, Bone Substitutes, Ceramics, Cholesterol, Culture Media, Conditioned, Glass, Humans, Lipids, Materials Testing, Membrane Microdomains, Mesenchymal Stem Cells, Mevalonic Acid, Microarray Analysis, Myosins, Phosphorylation, Proteins, RNA, Messenger, Spectrum Analysis, Raman, Strontium, Up-Regulation