Programming cell growth into different cluster shapes using diffusible signals

• Main Authors: Brenner, M.P (Author), Guo, Y. (Author), Nitzan, M. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: animal; Animals; Article; biological model; biology; cell aggregation; Cell Aggregation; cell communication; Cell Communication; cell growth; cell migration; cell proliferation; Cell Proliferation; cell reprogramming technique; cell shape; Cell Shape; cell structure; cell surface; Cell Surface Extensions; Cellular Reprogramming Techniques; Computational Biology; computer simulation; Computer Simulation; gene regulatory network; Gene Regulatory Networks; genetic engineering; Genetic Engineering; growth inhibitor; Growth Inhibitors; growth rate; human; Humans; mathematical model; Models, Biological; morphogenesis; Morphogenesis; physiology; procedures; signal transduction; synthetic biology; Synthetic Biology
• Online Access: View Fulltext in Publisher

 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. Copyright © 2021 Guo et al.