Mechanotransduction Across Time and Length Scales

Abstract

Mechanotransduction is a process that spans both time and length scales, from the nanoscale machines that sense substrate properties, to the morphogenesis and healing of whole organs. Studies of mechanotransduction have generated a wealth of knowledge about the mechanisms of the transmission of mechanical cues and their downstream effects, but these studies have largely been limited in the scope of key experimental parameters and outputs. A more comprehensive view of the mechanisms and implications of mechanotransduction would aid in the design of new therapies to leverage these phenomena. Here, we seek to broaden not only the view of the material parameters that cells can sense, but also the scope of the outputs of this sensing. We first focus on a relatively underexplored material property, stress relaxation, and show that stress relaxation can induce counterintuitive behaviors via the simple clutch mechanism of mechanosensing. We then exploit cells’ response to stress relaxation, showing that stress relaxation can be used to tune healing for bone tissue engineering. To integrate this complexity into a coherent picture, we then perform a global transcriptomic analysis of substrate sensing, uncovering relationships between the sensing of different material properties and exploring the extent of their downstream effects. Finally, given these developments in understanding the complexity of cell-material interactions, we propose a biomaterial design methodology to fully leverage this complexity to maximize functionality of therapeutic biomaterials.