Toward a modular analysis of cell mechanosensing and mechanotransduction: A manual for cell mechanics

Introduction: Cellular mechanosensing and -transduction are critical functions in the shaping of cells and tissues. Although an increasing literature details the proteins and complexes involved in mechanotransduction, how these mechanisms generate the mechanochemical functions of cell motility is often poorly understood. This is a result of the fact that cells can exhibit a number of different types of motility depending on factors such as cell type and local chemical and mechanical perturbations. Due to these factors, even a genetically homogeneous cell population presents a confusing array of different motility phenotypes to the experimentalist. Therefore, we suggest a new approach to understanding cell mechanical functions through reverse systems engineering. Through quantitative analysis, we have observed that, though motility over a population of cells is heterogeneous, at a particular time and location at the cell edge, a cell exhibits only one of a limited number of modular, morphodynamic states of the acto-myosin cytoskeleton. Furthermore, a single motility module can exhibit a heterogeneous cycle of individual steps, with chemical and mechanical interactions changing over the course of this cycle. Thus, much in the way an engineer would describe the functions of components in a car engine, we should be able to approach many problems in cell motility by first describing the molecular steps involved in the basic motility modules and then showing how signaling pathways regulate those modules in order to perform cell-wide functions. In the case of cell motility, we believe there are less than thirty distinct motility modules. With a detailed, quantitative understanding of normal cell motility functions, it will be possible to understand how their malfunction can result in disease processes and to develop therapies that target specific motility modules.