论文标题
机械反馈在调节增长的多细胞球体的大小中
Mechanical Feedback in Regulating the Size of Growing Multicellular Spheroids
论文作者
论文摘要
细胞测量其嵌入器官的维度的机制，并在达到最终大小时减慢其生长，这是一个长期存在的发育生物学问题。力学在此反馈中的作用被认为很重要。形态弹性是建模生长弹性组织的标准连续框架。但是，在这种理论中，在没有其他变量的情况下，生长和机械应力之间的反馈会导致组织的塌陷或无限生长，但通常禁止达到有限的渐近尺寸（“大小控制”）。在本文中，我们修改了这种经典环境，以包括与增长相关的充满活力的成本，从而导致尺寸控制的物理效果。本模型同时提供了定性正确的残余应力曲线，并具有自然出现的坏死核，所有这些核心以前曾在多细胞球体中实验建立。这是通过从热力学框架中得出的局部反馈机制来实现的。该模型为实验系统提供了可测试的预测，并且可能是迈向理解力学在多方面的问题中的作用的一步，即增长器官如何达到其最终尺寸。
The mechanism by which cells measure the dimension of the organ in which they are embedded, and slow down their growth when the final size is reached, is a long-standing problem of developmental biology. The role of mechanics in this feedback is considered important. Morphoelasticity is a standard continuum framework for modeling growing elastic tissues. However, in this theory, in the absence of additional variables, the feedback between growth and mechanical stress leads to either a collapse or unbounded growth of the tissue, but usually prohibits reaching a finite asymptotic size ('size control'). In this article, we modify this classical setting to include an energetic cost associated with growth, leading to the physical effect of size control. The present model simultaneously provides a qualitatively correct residual stress profile and has a naturally emerging necrotic core, all of which have previously been experimentally established in multicellular spheroids. This is achieved through a local feedback mechanism derived from a thermodynamical framework. The model delivers testable predictions for experimental systems and could be a step towards the understanding of the role of mechanics in the multifaceted question of how growing organs attain their final size.
