title: Microelastic mapping of the rat dentate gyrus.
abstract: The lineage commitment of many cultured stem cells, including adult neural stem cells (NSCs), is strongly sensitive to the stiffness of the underlying extracellular matrix. However, it remains unclear how well the stiffness ranges explored in culture align with the microscale stiffness values stem cells actually encounter within their endogenous tissue niches. To address this question in the context of hippocampal NSCs, we used atomic force microscopy to spatially map the microscale elastic modulus (E) of specific anatomical substructures within living slices of rat dentate gyrus in which NSCs reside during lineage commitment in vivo. We measured depth-dependent apparent E-values at locations across the hilus (H), subgranular zone (SGZ) and granule cell layer (GCL) and found a two- to threefold increase in stiffness at 500 nm indentation from the H (49 ± 7 Pa) and SGZ (58 ± 8 Pa) to the GCL (115 ± 18 Pa), a fold change in stiffness we have previously found functionally relevant in culture. Additionally, E exhibits nonlinearity with depth, increasing significantly for indentations larger than 1 µm and most pronounced in the GCL. The methodological advances implemented for these measurements allow the quantification of the elastic properties of hippocampal NSC niche at unprecedented spatial resolution.
authors.affiliation: Unit of Biophysics and Bioengineering, School of Medicine, University of Barcelona , Barcelona , Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Luque
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; UC Berkeley - UCSF Graduate Program in Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Michael S
authors.identifier: 0000-0002-7316-778X
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
keywords: atomic force microscopy; elastic modulus; hippocampus; neural stem cells