This program of five seed projects constitutes the start of a joint approach towards identifying the connection between stiffness and function of cancer cells. The projects tie in with two strong research lines within the CRCG dealing with distinctly different kinds of cancer —leukemia and glioblastoma —headed by prof. J.J. Schuringa and prof. F.A.E. Kruyt, respectively. In addition to the clinical relevance of each of these, the combination allows us to resolve the seemingly opposite stiffening trends in leukemia versus glioblastoma cells.
The program is organized along the structure—property—function axis comprises a set of five experimental/computational projects that use different methods to interrogate the key microstructural elements and to measure mechanical properties. Function in this context refers to oncogenic properties, which will be investigated by studying patient samples as well as CRISPR-Cas models with known oncogenes, and by investigating the localization of the nanosensor YAP. These aspects will be studied while modulating the composition of the TME, the stiffness of hydrogel ECM-mimics, the hypoxic conditions and the extent of applied external stress. Concurrently, and in close interaction with the experimental studies, a computational mechanotransduction model will be developed to capture the quantitative structure—stiffness relationship, while molecular dynamics (MD) simulations will be performed of the force-dependent localization of YAP.