7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
The Mechanical Control of CNS Development and Disease
University of Cambridge Department of Physiology, Development and Neuroscience, Downing Street Anatomy Building, Cambridge CB2 3DY UK
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During the development of the nervous system, neurons migrate and grow over great distances. During these processes, they are exposed to a multitude of signals determining how they grow. Currently, our understanding of neuronal development and function is, in large part, based on studies of biochemical signaling. Despite the fact that forces are involved in any kind of cell motion, mechanical aspects have so far rarely been considered. Here we show how Xenopus neurons respond to their mechanical environment. Axonal growth patterns in vitro strongly depended on substrate stiffness. In vivo atomic force microscopy measurements revealed stiffness gradients in developing brain tissue, which axons followed towards soft. This turning away from stiffer substrates was reproduced in vitro – in the absence of chemical gradients. Globally and locally interfering with brain stiffness, blocking mechanotransduction pharmacologically, and knockdown of the mechanosensitive ion channels Piezo1 in vivo all led to similar aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors, strongly suggesting that neuronal growth is not only controlled by chemical signals – as it is currently assumed – but also by the tissue’s local mechanical properties. Importantly, the mechanics of CNS tissue changed after mechanical trauma and demyelination. Furthermore, primary human glioblastoma cells showed distinct mechanical features depending on their location within the tumor. Our results thus suggest an important role of mechanical signals in health and disease of the nervous system.