Inferring epithelial tissue mechanics through data-efficient multi-fidelity modelling

我们体内的器官是如何控制它们的形状和结构的？我们知道，如果他们做不到这一点，我们就会过度生长，经常会患上癌症。如果我们能够了解这些控制系统，也许我们就能够了解当组织失去正确结构时会发生什么，并继续开发更有效的治疗方法。组织结构的适当控制是由于组成组织的细胞内部和细胞之间的机械力的平衡。因此，量化细胞和组织的力学对于了解它们的形状和结构是至关重要的。最近，我们的团队成员制作了一组大型图像和视频，展示了在实验室中，一种特殊类型的组织是如何形成一张强烈附着于相邻细胞的单层细胞的。我们还创建了一个计算机模型，使我们能够探索机械力的不同平衡如何导致这片细胞具有不同的形状和结构。然而，很难从图像中准确地确定模型中每个机械力的强度，因为模型需要一段时间才能运行。在这个项目中，我们将使用新的和现有的人工智能和机器学习方法来更快地从我们的数据中学习这些机械特性，方法是以自动的方式收集从我们的模型的简单版本中收集的信息。因此，我们将对这些机械性能做出更好的估计，并更好地了解细胞片如何获得其特有的形状和结构。我们将编写软件来完成这项工作，其他科学家也可以使用这些软件来研究从细胞和发育生物学到合成生物学、再生医学和癌症研究等生物学领域的类似问题。

How do the organs in our body control their shape and structure? We know that when they fail to do this, we get overgrowth, and frequently cancer. If we can understand these control systems, perhaps we will be able to understand what happens when tissues lose their correct structure, and go on to develop more effective treatments. Proper control of tissue structure comes about due to a balance of mechanical forces acting within, and between, the cells that make up a tissue. Therefore, quantifying the mechanics of cells and tissues is essential to understanding their shape and structure.Recently, our team members generated a large set of images and videos showing how, in the lab, a special type of tissue forms a single sheet of cells strongly adhering to their neighbours. We also created a computer model that allowed us to explore how different balances of mechanical forces can lead to this sheet of cells having different shapes and structures. However, it is difficult to precisely pin down the strength of each mechanical force in the model from the images, because it takes a while for the model to run.In this project, we will use new and existing artificial intelligence and machine learning methods to learn these mechanical properties much faster from our data, by bringing together information gleaned from simpler versions of our model in an automated way. As a result, we will come up with better estimates for these mechanical properties, and a better understanding of how cell sheets attain their characteristic shapes and structures. We will write software to do this that can also be used by other scientists studying similar problems in areas of biology ranging from cell and developmental biology to synthetic biology, regenerative medicine, and cancer research.