Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, United States.
Elife. 2023 Oct 2;12:e85569. doi: 10.7554/eLife.85569.
In order to understand morphogenesis, it is necessary to know the material properties or forces shaping the living tissue. In spite of this need, very few in vivo measurements are currently available. Here, using the early embryo as a model, we describe a novel cantilever-based technique which allows for the simultaneous quantification of applied force and tissue displacement in a living embryo. By analyzing data from a series of experiments in which embryonic epithelium is subjected to developmentally relevant perturbations, we conclude that the response to applied force is adiabatic and is dominated by elastic forces and geometric constraints, or system size effects. Crucially, computational modeling of the experimental data indicated that the apical surface of the epithelium must be softer than the basal surface, a result which we confirmed experimentally. Further, we used the combination of experimental data and comprehensive computational model to estimate the elastic modulus of the apical surface and set a lower bound on the elastic modulus of the basal surface. More generally, our investigations revealed important general features that we believe should be more widely addressed when quantitatively modeling tissue mechanics in any system. Specifically, different compartments of the same cell can have very different mechanical properties; when they do, they can contribute differently to different mechanical stimuli and cannot be merely averaged together. Additionally, tissue geometry can play a substantial role in mechanical response, and cannot be neglected.
为了理解形态发生,有必要了解塑造活组织的物质特性或力。尽管有此需求,但目前可用的体内测量非常少。在这里,我们使用早期胚胎作为模型,描述了一种新的基于悬臂的技术,该技术可同时定量测量活胚胎中的施加力和组织位移。通过分析一系列实验中的数据,这些实验使胚胎上皮细胞受到与发育相关的干扰,我们得出的结论是,对施加力的响应是绝热的,主要由弹性力和几何约束或系统尺寸效应决定。至关重要的是,对实验数据的计算模型表明,上皮细胞的顶端表面必须比基底表面更软,这一结果我们通过实验得到了证实。此外,我们还使用实验数据和全面的计算模型来估算顶端表面的弹性模量,并设定了基底表面的弹性模量的下限。更一般地,我们的研究揭示了一些重要的普遍特征,我们认为在任何系统中对组织力学进行定量建模时都应更广泛地考虑这些特征。具体而言,同一细胞的不同隔室可以具有非常不同的机械特性;当它们具有不同的机械特性时,它们可以对不同的机械刺激做出不同的贡献,而不能简单地平均在一起。此外,组织几何形状可以在机械响应中起重要作用,并且不能忽略。