Mechanosensing of glial cells triggers immune response in the CNS
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. We have shown 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’~100Pa) to shear moduli G’≥10kPa 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. This surprising result could explain how engineered bioinert in vitro polymers can trigger robust inflammatory reactions in vivo. Furthermore, information of the underlying molecular and biophysical mechanism could aid in the rational design of implants and biomaterials, enable pharmacological control against mechanosensitive pathways, and have further implications in the crosstalk between immune cells and their mechanical environment.
Bio
Dr. Jochen Guck received his PhD in Physics from the University of Texas at Austin in 2001. After several years as a group leader at the University of Leipzig (Germany), he moved to the Cavendish Laboratory of the University of Cambridge as a Lecturer in 2007 and was promoted to Reader in Biophysics in 2009. Since 2012 he is Professor of Cellular Machines at the Biotechnology Center of the Technische Universität Dresden (Germany). His research centers on exploring the global physical properties of biological cells and tissues and their importance for the cells` function and behavior. He also develops novel photonic, microfluidic and scanning-force probe techniques for the study of these optical and mechanical properties. The ultimate goal is utilizing this insight for novel diagnostic and therapeutic approaches. His work has been recognized by several awards, amongst them the Cozzarelli Award of the National Academy of Sciences in 2008, the Paterson Prize and Medal of the Institute of Physics in 2011 and an Alexander-von-Humboldt Professorship in 2012.