title: Compression stiffening of brain and its effect on mechanosensing by glioma cells.
abstract: Many cell types, including neurons, astrocytes and other cells of the central nervous system respond to changes in extracellular matrix or substrate viscoelasticity, and increased tissue stiffness is a hallmark of several disease states including fibrosis and some types of cancers. Whether the malignant tissue in brain, an organ that lacks the protein-based filamentous extracellular matrix of other organs, exhibits the same macroscopic stiffening characteristic of breast, colon, pancreatic, and other tumors is not known. In this study we show that glioma cells like normal astrocytes, respond strongly in vitro to substrate stiffness in the range of 100 to 2000 Pa, but that macroscopic (mm to cm) tissue samples isolated from human glioma tumors have elastic moduli on the order of 200 Pa that are indistinguishable from those of normal brain. However, both normal brain and glioma tissues increase their shear elastic moduli under modest uniaxial compression, and glioma tissue stiffens more strongly under compression than does normal brain. These findings suggest that local tissue stiffness has the potential to alter glial cell function, and that stiffness changes in brain tumors might arise not from increased deposition or crosslinking of collagen-rich extracellular matrix but from pressure gradients that form within the tumors in vivo.
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA ; The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pogoda
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA.
authors.forename: LiKang
authors.initials: L
authors.lastname: Chin
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA.
authors.forename: Penelope C
authors.initials: PC
authors.lastname: Georges
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA.
authors.forename: FitzRoy J
authors.initials: FJ
authors.lastname: Byfield
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA ; The Faculty of Health Sciences of the Jan Kochanowski University, Kielce, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Bucki
authors.affiliation: Department of Neurosurgery, Temple University Hospital, Philadelphia, PA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Temple University Hospital, Philadelphia, PA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weaver
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Wells
authors.affiliation: CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
authors.forename: Cezary
authors.initials: C
authors.lastname: Marcinkiewicz
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA ; Departments of Physiology and Physics & Astronomy, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
keywords: astrocyte; brain rheology; glioma; mechanosensing; viscoelasticity
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