The role of mechanics in cell culture for micro-tissue fabrication. A model-based study using self-propelled particles

In tissue engineering, stem cells are used to produce artificial constructs that can improve or replace biological tissue. The production of these constructs often involves a cell culture step, in which cells are multiplied and assembled in ‘micro-tissues’ with desired tissue properties. To ensure product quality, the physical micro-environment of single cells must be well-controlled during this step. Yet, the formation of this micro-environment originates from cell-intrinsic and self-regulating mechanisms which are not well understood. This project aims to understand and quantify the self-regulated mechanical state that is established by cells in cell culture systems. For this, we will make computational models using self-propelled particles that capture the active processes (such as proliferation, migration and apoptosis) that govern the mechanical outcome at long timescales. These outcomes will be compared to continuum ‘active gel’ models that capture mechanical behavior in effective hydrodynamic material properties. In a second step, and using this information, we will construct a smaller-scale, but more detailed particle-based model that can quantify the mechanical micro-environment of individual cells. With this model we will be able to investigate how culture system process settings can be modified in order to guide the mechanical micro-environment (and eventually, cell fate) in cell cultures for tissue engineering applications.