| Abstract: |
| Growth regulation and pattern formation are two main problems in developmental biology. How cells know when to stop growing at certain tissue size with specific shape is an important question in both developmental biology and regenerative medicine, and it is still an unsolved mystery in many systems. During the growth, tissues and organs always exhibit self-government to some extent. Cells stop proliferation precisely when the intended size of the tissue or organ is achieved. Meanwhile, differential cell shapes in space are integrated to give rise to well-organized overall structure. Uncontrolled growth of the cells in tissues or organs will lead to abnormal development or fatal diseases such as cancer. Therefore, developing an extensible predictive mathematical model for exploring the mechanisms involved in the tissue development is significant for understanding the fundamental principles in developmental biology, with a broad range of applications from tissue engineering to biomanufacturing and biotech industry. Experimental data suggests that mechanical properties of cells and chemical signals in both intracellular and extracellular domains play critical roles in size control and shape formation. Here we develop a multi-scale, mechochemical coupled model of tissue growth control. This first-of-class modeling approach provides sub-cellular details to both mechanical properties and chemical signaling during tissue growth. This model is applied to test competing hypotheses in the field to resolve the highly debated question of how tissues reach their final size, as well as how the tissue shape is determined simultaneously. |
|