Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey.
Biophys J. 2012 Jul 3;103(1):152-62. doi: 10.1016/j.bpj.2012.05.048.
Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes.
理解物理信号如何指导生物过程，需要定性和定量了解细胞在生理上逼真的三维 (3D) 环境中产生和感知的机械力。在这里，我们使用计算建模和工程化的具有精确几何形状的上皮组织，定义了直接测量嵌入天然 I 型胶原中的 3D 组织机械应力分布所需的实验参数。我们发现，为了在这些环境中准确计算应力，我们必须考虑基质中的力学异质性，我们使用共聚焦反射和原子力显微镜对其进行可视化和量化。使用这种技术，我们能够在细胞上皮-基质界面获得牵引力，并解析和量化整个周围基质中的力学应力模式。我们发现，虽然单个细胞通过收缩和拉动基质来产生张力，但多细胞组织的收缩也可以对基质施加压力，导致出现压缩。此外，组织几何形状决定了机械应力在整个上皮组织中的空间分布，这种分布通过跨越数百微米的距离进行机械传递。空间分辨力的力学图谱可以深入了解在正常和病理过程中，多细胞组织感知和解释的物理参数的类型和大小。
