To discern how mechanical forces coordinate biological outcomes, methods that map cell-generated forces in a spatiotemporal manner, and at cellular length scales, are critical. In their native environment, whether it be within compact multicellular three-dimensional structures or sparsely populated fibrillar networks of the extracellular matrix, cells are constantly exposed to a slew of physical forces acting on them from all directions. At the same time, cells exert highly localized forces of their own on their surroundings and on neighboring cells. Together, the generation and transmission of these forces can control diverse cellular activities and behavior as well as influence cell fate decisions. To thoroughly understand these processes, we must first be able to characterize and measure such forces. However, our experimental needs and technical capabilities are in discord—while it is apparent that we should study cell-generated forces within more biologically relevant 3D environments, this goal remains challenging because of caveats associated with complex “sensing–transduction–readout” modalities. In this Review, we will discuss the latest techniques for measuring cell-generated forces. We will highlight recent advances in traction force microscopy and examine new alternative approaches for quantifying cell-generated forces, both of individual cells and within 3D tissues. Finally, we will explore the future direction of novel cellular force-sensing tools in the context of mechanobiology and next-generation biomaterials design.

中文翻译：

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可视化和量化细胞产生力的物理化学工具。

为了辨别机械力如何协调生物学结果，以时空方式在细胞长度尺度上绘制细胞产生的力的方法至关重要。在原始环境中，无论是处于紧凑的多细胞三维结构中还是位于细胞外基质的稀疏纤维状网络中，细胞都不断受到来自各个方向作用于其上的一系列物理力的作用。同时，细胞在周围环境和邻近细胞上施加自身高度局部化的力。这些力的产生和传递可以共同控制各种细胞活动和行为，并影响细胞命运的决定。为了彻底理解这些过程，我们必须首先能够表征和测量这种作用力。然而，我们的实验需求和技术能力并不协调-虽然很明显，我们应该在更生物学相关的3D环境中研究细胞产生的力，但是由于与复杂的“传感-传导-读出”方式有关的警告，该目标仍然具有挑战性。在这篇综述中，我们将讨论测量细胞产生力的最新技术。我们将重点介绍牵引力显微镜的最新进展，并研究量化细胞生成力的新替代方法，无论是单个细胞还是3D组织内。最后，我们将在机械生物学和下一代生物材料设计的背景下探索新型细胞力传感工具的未来方向。