Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827.
Department of Chemistry, Rice University, Houston, TX 77005-1827.
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4288-4293. doi: 10.1073/pnas.1706920115. Epub 2018 Apr 2.
Cell fate determination is typically regulated by biological networks, yet increasing evidences suggest that cell-cell communication and environmental stresses play crucial roles in the behavior of a cell population. A recent microfluidic experiment showed that the metabolic codependence of two cell populations generates a collective oscillatory dynamic during the expansion of a biofilm. We develop a modeling framework for the spatiotemporal dynamics of the associated metabolic circuit for cells in a colony. We elucidate the role of metabolite diffusion and the need of two distinct cell populations to observe oscillations. Uniquely, this description captures the onset and thereafter stable oscillatory dynamics during expansion and predicts the existence of damping oscillations under various environmental conditions. This modeling scheme provides insights to understand how cells integrate the information from external signaling and cell-cell communication to determine the optimal survival strategy and/or maximize cell fitness in a multicellular system.
细胞命运的决定通常受到生物网络的调控，但越来越多的证据表明，细胞间通讯和环境应激在细胞群体的行为中起着至关重要的作用。最近的一项微流控实验表明，两种细胞群体的代谢相互依存性在生物膜的扩展过程中产生了集体振荡动态。我们为菌落中细胞的相关代谢回路的时空动态开发了一个建模框架。我们阐明了代谢物扩散的作用以及观察振荡需要两个不同细胞群体的必要性。独特的是，这种描述捕捉到了扩展过程中振荡的开始和此后的稳定动态，并预测了在各种环境条件下阻尼振荡的存在。这种建模方案提供了深入了解细胞如何整合来自外部信号和细胞间通讯的信息，以确定在多细胞系统中最佳的生存策略和/或最大限度地提高细胞适应性的见解。
