生长中多细胞球尺寸调控的力学反馈机制
Mechanical Feedback in Regulating the Size of Growing Multicellular Spheroids
AI总结：
针对发育生物学中细胞感知器官尺寸并调控生长的难题，本研究在形态弹性力学框架中引入生长能量损耗，构建出可实现多细胞球尺寸调控、符合残余应力分布且自然出现坏死核心的模型，为理解器官尺寸调控的力学机制提供新思路。
摘要：
细胞如何感知其所在器官的尺寸，并在器官达到最终大小时减缓生长，是发育生物学中一个长期存在的难题。力学在这一反馈过程中的作用被认为十分重要。形态弹性力学（Morphoelasticity）是模拟生长弹性组织的标准连续介质框架。然而，在该理论中，若不引入额外变量，生长与机械应力之间的反馈会导致组织塌陷或无限生长，通常无法实现有限渐近尺寸（即“尺寸调控”）。本文对这一经典框架进行了修改，引入了与生长相关的能量损耗，从而产生尺寸调控的物理效应。本模型同时给出了定性正确的残余应力分布，并且自然出现了坏死核心，这些特征均已在多细胞球的实验中得到证实。该模型通过源自热力学框架的局部反馈机制实现上述结果，可为实验系统提供可验证的预测，也可为理解力学在生长器官如何达到最终尺寸这一复杂问题中的作用提供参考。
英文摘要：
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.
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