Brain extracellular matrix mechanics across scales
Our cells are held in place by a matrix of fibers. In cancer, this matrix changes and typically becomes stiffer, helping tumors grow and spread. In most organs, this stiffening comes from collagen. But the brain is different: it is remarkably soft, and its matrix contains almost no collagen. Instead, it is built mainly from a sugar-based molecule called hyaluronic acid, together with other molecules.
In this thesis, computer simulations were used to study how the molecules in the brain-specific matrix behave, including how they stretch and interconnect, and how this shapes the stiffness of brain tissue. Simplified computational models were built for each component of this matrix and then combined into a virtual network resembling real brain tissue.
By comparing a "healthy" version of this network to a denser one, similar to a brain tumor, it became possible to test whether the changes seen in tumors are enough to explain how much stiffer cancerous brain tissue becomes. The stiffness of the healthy network matched real experimental measurements well, but the dense network was not as stiff as observed in tumors, suggesting that other factors, not modelled here, also contribute to tumor stiffening. These models offer a new tool for studying how this matrix in the brain changes in cancer.