Cell death as a trigger for morphogenesis

The complex morphologies observed in many biofilms play a critical role in the survival of these microbial communities. Recently, the formation of wrinkles has been the focus of many studies aimed at finding fundamental information on morphogenesis during development. While the underlying genetic mechanisms of wrinkling are not well-understood, recent discoveries have led to the counterintuitive idea that wrinkle formation is triggered by localized cell death. This work examines the hypothesis that the material properties of a biofilm both power and control wrinkle formation within biofilms in response to localized cell death. Using an agent-based model and a high-performance platform (Biocellion), we built a model that qualitatively reproduced wrinkle formation in biofilms due to cell death. Through the use of computational simulations, we determined important relationships between cellular level mechanical interactions and changes in colony morphology. These simulations were also used to identify significant cellular interactions that are required for wrinkle formation. These results are a first step towards more comprehensive models that, in combination with experimental observations, will improve our understanding of the morphological development of bacterial biofilms.

诸多生物被膜（biofilm）中观察到的复杂形态结构，对这些微生物群落的存活起着至关重要的作用。近年来，褶皱形成一直是众多研究的核心议题，这些研究旨在探索发育过程中形态发生的基础机制。尽管人们对褶皱形成的潜在遗传机制尚不完全明晰，但最新研究发现提出了一个反直觉的观点：褶皱形成由局部细胞死亡触发。本研究验证了这样一项假说：生物被膜的材料特性既为响应局部细胞死亡的生物被膜内褶皱形成提供动力，又对其加以调控。本研究借助基于智能体的模型与高性能平台Biocellion，构建了一个可定性复现细胞死亡引发的生物被膜褶皱形成过程的模型。通过计算模拟，本研究明确了细胞层面的力学相互作用与菌落形态变化之间的关键关联。同时，本研究还通过这些模拟确定了褶皱形成所必需的关键细胞相互作用机制。本研究成果是构建更完善模型的第一步，后续结合实验观测，将有助于我们更深入地理解细菌生物被膜的形态发育过程。