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Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

Author(s)
Zeiger, Adam Scott; Loe, Felicia C.; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J. Van
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Abstract
Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.
Date issued
2012-05
URI
http://hdl.handle.net/1721.1/71642
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Zeiger, Adam S. et al. “Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior.” Ed. Effie C. Tsilibary. PLoS ONE 7.5 (2012): e37904.
Version: Final published version
ISSN
1932-6203

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