I seek to understand the molecular origin of cell mechanosensing - the ability of biological cells to sense and respond to the mechanical properties of their environment. Moreover, I want to explore the possibility that propagation of mechanical deformation within soft biomaterials can act as a communication route between neighboring cells. A long term goal is to guide injured axons to establish reconnection with the proper target by directing the axon towards the mechanical deformations generated by the target cell. ‘Cell mechanosensing’ raises some basic science questions, part of which can only be solved by an interdisciplinary-multi-scale approach, combining concepts from macroscopic approaches - such as elasticity theory and rheology - with a molecular point of view, taking into account the intricate interplay of chemical and physical processes. We will use a unique combination of high resolution optical microscopy, single molecule imaging, magnetic tweezers, biomaterial design and characterization, numerical algorithms and theoretical modeling. In particular, our aims include: 1. Characterization of the force generated by neuronal growth cone and its frequency, before and following injury.2.Developing new engineered protein biomaterials with mechano-sensitive properties and a well defined dynamic viscoelastic profile which are able to support neuronal cell growth. These include biomaterials which: a) Change their fluorescence properties in response to small material deformations in the nanometer range. b) Efficiently propagate and amplify growth-cone-generated mechanical deformations to allow for cell-cell communication. An essential part of this project is studying the dependence of the viscoelastic spectrum of the network on the mechanical properties of the single chain. 3. Identifying the feedback mechanism that enables the cell to regulate its intrinsic elasticity and the forces it applies in response to the mechanical properties of the substrate.