title: Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans.
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.
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Louis T
authors.initials: LT
authors.lastname: McLane
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Fogg
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Scrimgeour
authors.affiliation: 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.
authors.forename: Johnna S
authors.initials: JS
authors.lastname: Temenoff
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Anna
authors.initials: A
authors.lastname: Granqvist
authors.affiliation: 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.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Curtis
mesh_terms: D053674:Aggrecans / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D004058:Diffusion; D005109:Extracellular Matrix / Q000378:metabolism* / Q000382:microbiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D053758:Nanoparticles / Q000378:metabolism; D052898:Optical Tweezers; D016062:Porosity; D011514:Proteus vulgaris; D051381:Rats; D055672:Static Electricity
chemical_list: D053674:Aggrecans; D001426:Bacterial Proteins; D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid; D019765:Chondroitin ABC Lyase