Auxetic nuclei in embryonic stem cells exiting pluripotency
Stefano Pagliara,
Kristian Franze,
Crystal R. McClain,
George Wylde,
Cynthia L. Fisher,
Robin J. M. Franklin,
Alexandre J. Kabla,
Ulrich F. Keyser,
Kevin J. Chalut
Embryonic stem cells (ESCs) self-renew in a state of naïve pluripotency in which they are competent to generate all somatic cells. It has been hypothesized that, before irreversibly committing, ESCs pass through at least one metastable transition state. This transition would represent a gateway for differentiation and reprogramming of somatic cells. Here, we show that during the transition, the nuclei of ESCs are auxetic: they exhibit a cross-sectional expansion when stretched and a cross-sectional contraction when compressed, and their stiffness increases under compression. We also show that the auxetic phenotype of transition ESC nuclei is driven at least in part by global chromatin decondensation. Through the regulation of molecular turnover in the differentiating nucleus by external forces, auxeticity could be a key element in mechanotransduction. Our findings highlight the importance of nuclear structure in the regulation of differentiation and reprogramming.
The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system
Pouria Moshayedi,
Gilbert Ng,
Jessica C. F. Kwok,
Giles S. H. Yeo,
Clare E. Bryant,
James W. Fawcett,
Kristian Franze,
Jochen Guck
BIOMATERIALS
35
(13)
3919-3925
(2014)
| Journal
| PDF
Devices implanted into the body become encapsulated due to a foreign body reaction. In the central nervous system (CNS), this can lead to loss of functionality in electrodes used to treat disorders. Around CNS implants, glial cells are activated, undergo gliosis and ultimately encapsulate the electrodes. The primary cause of this reaction is unknown. Here we show that the mechanical mismatch between nervous tissue and electrodes activates glial cells. Both primary rat microglial cells and astrocytes responded to increasing the contact stiffness from physiological values (G' similar to 100 Pa) to shear moduli G' >= 10 kPa by changes in morphology and upregulation of inflammatory genes and proteins. Upon implantation of composite foreign bodies into rat brains, foreign body reactions were significantly enhanced around their stiff portions in vivo. Our results indicate that CNS glial cells respond to mechanical cues, and suggest that adapting the surface stiffness of neural implants to that of nervous tissue could minimize adverse reactions and improve biocompatibility. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.
Contact
Neuronal Mechanics Division Prof. Kristian Franze Principal Investigator
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
