3D CELL SHAPE AND CELL FATE ARE REGULATED BY THE DYNAMIC MICROMECHANICAL PROPERTIES OF THE CELL-ECM INTERFACE

摘要

Mechanobiology is an interdisciplinary field that focuses on predicting and understanding cellular responses to mechanical loads. The extracellular matrix (ECM) represents a macromolecular framework that naturally imparts structural support and spatial organization for resident cells. The ECM also participates in the communication and transfer of mechanical loads to cells, in part, via integrin attachment to the cytoskeleton (CSK). Recently, using a tissue model in which cells are embedded in a 3D collagen ECM, we have shown that fundamental cell behaviors, including morphology, proliferation, contractility, and ECM remodeling properties, can be modulated by varying 3D microstructural organization and mechanical properties of the surrounding collagen fibrils[1]. While these and other results demonstrate the critical role played by the ECM in regulating cell behavior, the mechanical-based mechanisms underlying these critical cell-ECM interactions have yet to be fully elucidated [2]. Models have been proposed, such as tensegrity, to explain the role of CSK elements, such as microtubules and microfilaments, in determining cell shape and mechanics[3]. Furthermore, this theoretical model has been insightful in the design and interpretation of experimental approaches to investigate signaling cascades and internal molecular deformations that result from mechanical perturbation of a cell. In fact, recent studies have documented that mechanical cues conveyed by changes in cell shape and the CSK induce distinct differentiation programs within multi-potential stem cells [4]. Interestingly, the majority of mechanobiology studies conducted to date do not focus on the encompassing ECM component of the cellular microenvironment. In fact, most studies evaluating cell-ECM interaction use a model system in which cells are grown on a planar, plastic surface coated with a specific ECM component. Unfortunately, such a model system does not accurately mimic the in vivo cellular microenvironment in which the cell is typically surrounded by and attached to a 3D network of collagen fibrils (Figure 1).