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Biophys J. 2016 Jun 21;110(12):2739-2750. doi: 10.1016/j.bpj.2016.05.027.

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans.

Author information

1
School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
2
School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas.
3
School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia; Department of Physics, Clarkson University, Potsdam, New York.
4
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia; W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia.
5
School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia. Electronic address: jennifer.curtis@physics.gatech.edu.

Abstract

The hyaluronan-rich pericellular matrix (PCM) plays physical and chemical roles in biological processes ranging from brain plasticity, to adhesion-dependent phenomena such as cell migration, to the onset of cancer. This study investigates how the spatial distribution of the large negatively charged bottlebrush proteoglycan, aggrecan, impacts PCM morphology and cell surface access. The highly localized pericellular milieu limits transport of nanoparticles in a size-dependent fashion and sequesters positively charged molecules on the highly sulfated side chains of aggrecan. Both rat chondrocyte and human mesenchymal stem cell PCMs possess many unused binding sites for aggrecan, showing a 2.5x increase in PCM thickness from ∼7 to ∼18 μm when provided exogenous aggrecan. Yet, full extension of the PCM occurs well below aggrecan saturation. Hence, cells equipped with hyaluronan-rich PCM can in principle manipulate surface accessibility or sequestration of molecules by tuning the bottlebrush proteoglycan content to alter PCM porosity and the number of electrostatic binding sites.

PMID:
27332132
PMCID:
PMC4919654
DOI:
10.1016/j.bpj.2016.05.027
[Indexed for MEDLINE]
Free PMC Article

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