Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

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 phy...

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Main Authors: Zeiger, Adam Scott, Loe, Felicia C., Li, Ran, Raghunath, Michael, Van Vliet, Krystyn J. Van
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Public Library of Science 2012
Online Access:http://hdl.handle.net/1721.1/71642
https://orcid.org/0000-0001-5735-0560
https://orcid.org/0000-0002-8537-8824
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author Zeiger, Adam Scott
Loe, Felicia C.
Li, Ran
Raghunath, Michael
Van Vliet, Krystyn J. Van
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Zeiger, Adam Scott
Loe, Felicia C.
Li, Ran
Raghunath, Michael
Van Vliet, Krystyn J. Van
author_sort Zeiger, Adam Scott
collection MIT
description 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.
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spelling mit-1721.1/716422022-09-23T12:53:16Z Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior Zeiger, Adam Scott Loe, Felicia C. Li, Ran Raghunath, Michael Van Vliet, Krystyn J. Van Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Van Vliet, Krystyn J. Zeiger, Adam Scott Loe, Felicia C. Li, Ran Raghunath, Michael Van Vliet, Krystyn J. 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. Massachusetts Institute of Technology. Singapore-MIT Alliance in Research and Technology (SMART) National Defense Science and Engineering Graduate Fellowship National Institutes of Health (U.S.). Molecular, Cell, and Tissue Biomechanics Training Grant (5T32EB006348-05) National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (DMR-0819762) National University of Singapore. Faculty Research Committee Grant National University of Singapore. Tissue Engineering Programme National Science Foundation (U.S.). (CAREER Award CBET-0644846) 2012-07-17T12:51:01Z 2012-07-17T12:51:01Z 2012-05 2012-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/71642 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. https://orcid.org/0000-0001-5735-0560 https://orcid.org/0000-0002-8537-8824 en_US http://dx.doi.org/10.1371/journal.pone.0037904 PLoS ONE Creative Commons Attribution application/pdf Public Library of Science PLoS
spellingShingle Zeiger, Adam Scott
Loe, Felicia C.
Li, Ran
Raghunath, Michael
Van Vliet, Krystyn J. Van
Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title_full Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title_fullStr Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title_full_unstemmed Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title_short Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior
title_sort macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior
url http://hdl.handle.net/1721.1/71642
https://orcid.org/0000-0001-5735-0560
https://orcid.org/0000-0002-8537-8824
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