Bridging the scales between single cell and tissue mechanics towards improved tumor diagnostics

• Applicants: Professor Dr. Sebastian Aland; Dr.-Ing. Anna Taubenberger
• Subject Area: Mechanics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511509575

Tumor mechanics is a promising biomarker for the prediction of patient outcome. Previous studies have either focused on whole tumor mechanics or single cancer cell mechanics and provide partly contradictory results. In fact, mechanical properties of tissues emerge by an intermixing of cellular active stresses (cellular surface tension and cell-cell adhesion) and passive stresses (viscoelasticity), making it yet unclear how to quantitatively relate experimental data of tissue to single cell mechanical results. The goal of this project is to close this gap by developing a continuum model of tumor tissue which describes the mechanical interactions of multiple cells, including cell surface tension, bending stiffness, viscoelasticity and cell-cell adhesion forces. The model will be combined with tailored experiments in which tumor spheroids are uniaxially compressed by atomic force microscopy (AFM). By comparing the force response to numerical results, the relative contributions of single cell rheological properties and cell-cell interactions can be deciphered, hence bridging the scales from single cell to tissue level mechanics. Validations will include systematic modulation of cell mechanics and adhesion by cytoskeletal drugs and genetic modifications. Finally, the model will be applied to the mechanical analysis of clinical tumor organoids and first data will be provided that can be correlated to clinical parameters. As a result, the method will not only lead to a deeper understanding of relevant parameters contributing to tumor mechanics, but enable a more profound use of single cancer cell mechanics as prognostic tool. Moreover, its versatility will be highly suitable towards further applications, e.g. to other tissue types and further developments towards the modeling of tumor growth.

• DFG Programme: Research Grants