Neuronal biomechanics measured using combined atomic force – traction force microscopy*

During brain development neurons grow axons and dendrites that extend from the cell body and connect with other neurons to form neuronal circuits. Axons navigate over long distances (10-100 times larger than the cell body) with remarkable precision, while interacting with an inhomogeneous and changing extracellular environment. Despite recent advances in our understanding of neuronal growth, the fundamental mechanisms that underlie the formation of functional connections between neurons are still poorly understood. In this talk I will present a novel experimental approach which integrates three different high – resolution techniques on the same platform, namely: traction force, fluorescence and atomic force microscopy. We use this powerful experimental platform to perform high – resolution measurements of the elastic modulus for cortical neurons. We relate the observed changes in cellular biomechanics with measured traction forces exerted by the axons on the growth substrate. In addition, we track individual components of the cell cytoskeleton and connect axonal dynamics with changes in the cytoskeleton, cellular volume, and elastic modulus. I will also present a theoretical model, based on elastic properties of biopolymer networks, that predicts simple power-law relationships between the measured biomechanical parameters. Our results demonstrate that neuronal growth is governed by a contact guidance mechanism, in which axons are guided by external biomechanical cues.