John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
Program in Biophysics, Harvard University, Boston, Massachusetts, United States of America.
PLoS Comput Biol. 2021 Nov 8;17(11):e1009576. doi: 10.1371/journal.pcbi.1009576. eCollection 2021 Nov.
Advances in genetic engineering technologies have allowed the construction of artificial genetic circuits, which have been used to generate spatial patterns of differential gene expression. However, the question of how cells can be programmed, and how complex the rules need to be, to achieve a desired tissue morphology has received less attention. Here, we address these questions by developing a mathematical model to study how cells can collectively grow into clusters with different structural morphologies by secreting diffusible signals that can influence cellular growth rates. We formulate how growth regulators can be used to control the formation of cellular protrusions and how the range of achievable structures scales with the number of distinct signals. We show that a single growth inhibitor is insufficient for the formation of multiple protrusions but may be achieved with multiple growth inhibitors, and that other types of signals can regulate the shape of protrusion tips. These examples illustrate how our approach could potentially be used to guide the design of regulatory circuits for achieving a desired target structure.
遗传工程技术的进步使得人工遗传电路的构建成为可能，这些电路已被用于产生差异基因表达的空间模式。然而，细胞如何被编程以及需要多复杂的规则才能实现所需的组织形态这一问题还没有得到太多关注。在这里，我们通过开发一个数学模型来研究细胞如何通过分泌可扩散信号来集体生长成具有不同结构形态的簇，这些信号可以影响细胞的生长速度。我们制定了如何使用生长调节剂来控制细胞突起的形成，以及在何种范围内可实现的结构与独特信号的数量成正比。我们表明，单个生长抑制剂不足以形成多个突起，但可能通过多个生长抑制剂来实现，并且其他类型的信号可以调节突起尖端的形状。这些例子说明了我们的方法如何可能用于指导设计监管电路以实现所需的目标结构。
