Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):7622-7632. doi: 10.1073/pnas.1919607117. Epub 2020 Mar 19.
During development, organisms acquire three-dimensional (3D) shapes with important physiological consequences. While basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat but later undergo a mechanical instability and become wrinkled. To gain mechanistic insights into this dynamic pattern-formation process, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the substrate, and the friction between them. Our model shows quantitative agreement with experimental measurements of biofilm expansion dynamics, and it accurately predicts two distinct spatiotemporal patterns observed in the experiments-the wrinkles initially appear either in the peripheral region and propagate inward (soft substrate/low friction) or in the central region and propagate outward (stiff substrate/high friction). Our results, which establish that nonuniform growth and friction are fundamental determinants of stress anisotropy and hence biofilm morphology, are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns. We discuss the implications of forming undulated biofilm morphologies, which may enhance the availability of nutrients and signaling molecules and serve as a "bet hedging" strategy.
在发育过程中，生物体获得具有重要生理后果的三维（3D）形状。虽然真核生物中已知形态发生的基本机制，但在体内操纵它们通常很困难。为了解决这个问题，我们在这里研究了在琼脂基质上生长的发育生物膜，通过改变琼脂浓度来改变其时空形态模式。扩展生物膜最初是平坦的，但后来会经历机械不稳定性并变得起皱。为了深入了解这种动态模式形成过程的机制，我们开发了一个模型，该模型考虑了营养物质的扩散及其被细菌的吸收、细菌的生长/生物膜基质的产生、生物膜和基质的机械变形以及它们之间的摩擦。我们的模型与生物膜扩展动力学的实验测量结果具有定量一致性，并且它准确地预测了实验中观察到的两种不同的时空模式——最初出现在外围区域并向内传播的皱纹（软基质/低摩擦）或出现在中心区域并向外传播的皱纹（硬基质/高摩擦）。我们的结果表明，非均匀生长和摩擦是各向异性和生物膜形态的基本决定因素，这广泛适用于具有类似形态的细菌生物膜，并为其他细菌生物膜如何形成不同的皱纹模式提供了深入了解。我们讨论了形成波浪形生物膜形态的意义，这可能会增加营养物质和信号分子的可用性，并作为一种“风险分散”策略。
