Allen Discovery Center at Tufts University, Medford, MA, 02155, USA.
Department of Biology, Tufts University, Medford, MA, 02155, USA; Allen Discovery Center at Tufts University, Medford, MA, 02155, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Biochem Biophys Res Commun. 2024 Oct 30;731:150396. doi: 10.1016/j.bbrc.2024.150396. Epub 2024 Jul 14.
Individual cells have numerous competencies in physiological and metabolic spaces. However, multicellular collectives can reliably navigate anatomical morphospace towards much larger, reliable endpoints. Understanding the robustness and control properties of this process is critical for evolutionary developmental biology, bioengineering, and regenerative medicine. One mechanism that has been proposed for enabling individual cells to coordinate toward specific morphological outcomes is the sharing of stress (where stress is a physiological parameter that reflects the current amount of error in the context of a homeostatic loop). Here, we construct and analyze a multiscale agent-based model of morphogenesis in which we quantitatively examine the impact of stress sharing on the ability to reach target morphology. We found that stress sharing improves the morphogenetic efficiency of multicellular collectives; populations with stress sharing reached anatomical targets faster. Moreover, stress sharing influenced the future fate of distant cells in the multi-cellular collective, enhancing cells' movement and their radius of influence, consistent with the hypothesis that stress sharing works to increase cohesiveness of collectives. During development, anatomical goal states could not be inferred from observation of stress states, revealing the limitations of knowledge of goals by an extern observer outside the system itself. Taken together, our analyses support an important role for stress sharing in natural and engineered systems that seek robust large-scale behaviors to emerge from the activity of their competent components.
个体细胞在生理和代谢空间中具有多种能力。然而，多细胞集体可以可靠地在解剖形态空间中导航，以达到更大、更可靠的终点。了解这个过程的稳健性和控制特性对于进化发育生物学、生物工程和再生医学至关重要。已经提出了一种使单个细胞能够协调特定形态结果的机制，即共享压力（其中压力是反映生理参数在稳态回路上下文中当前错误量的参数）。在这里，我们构建并分析了一个形态发生的多尺度基于代理的模型，在该模型中，我们定量研究了压力共享对达到目标形态的能力的影响。我们发现，压力共享提高了多细胞集体的形态发生效率；具有压力共享的群体更快地达到了解剖学目标。此外，压力共享影响多细胞集体中远处细胞的未来命运，增强了细胞的运动及其影响半径，这与压力共享可增加集体凝聚力的假设一致。在发育过程中，无法从观察压力状态来推断解剖学目标状态，这揭示了外部观察者对系统本身之外的目标知识的局限性。总之，我们的分析支持在自然和工程系统中压力共享的重要作用，这些系统寻求从其有能力的组件的活动中产生稳健的大规模行为。
