Project Details
Projekt
A01 Cell-microenvironment mechanical interactions in cancer from single cells to tissues
Applicants
Dr. Meritxell Huch; Dr.-Ing. Anna Taubenberger
Subject Area
Medical Physics, Biomedical Technology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 513752256
The complex environment in which tumors arise is characterized by altered mechanical properties compared to healthy tissues. These mechanical alterations are thought to be critical drivers of cancer progression, making tissue mechanical parameters promising biomarkers for better prediction of patient outcome. The mechanical changes occur across different scales, from single cells to the more complex tissue level context. To date, however, contributions of cell mechanical changes and collective cell behaviors to tumor tissue-scale mechanical characteristics -that can be measured by MR elastography (MRE) in a clinically more relevant setting- are not well described. We hypothesize that cell mechanical alterations occurring during cancer progression will influence tissue-scale mechanics. In this subproject we will quantitate the viscoelastic properties of patient-derived liver and pancreatic tumor tissues, isolated tumor cells and their derived organoid cultures using MRE using a range of state-of-the-art micro-mechanical methods, including atomic force microscopy (AFM), Brillouin microscopy, and real-time deformability cytometry (RT-DC). Thereby we aim to disentangle single cell contributions of the mechanical response of tumors tissues measured by novel wideband tabletop MRE technology. Tumor organoids will be cultured within tailored, mechanically and biochemically well-defined biomaterials, which will allow for systematic analysis of molecular contributors to microtissue mechanics and of the mechano-signaling machinery. By taking stromal interactions into account, the bioengineered model will be further extended towards more complex tissue surrogates. A01 will be central to this research unit as it exchanges expertise, materials and data in a bidirectional manner with other subprojects, for instance protocols for organoid cultures, bioengineered matrices of defined viscoelastic properties, and acquired biomechanical data from different techniques. Vice versa, A01 will highly benefit from the other projects with regards to data analysis, bioreactor design and MRE analysis. Specifically, with help of A03 we will be studying jamming-unjamming transitions in our bioengineered models and in collaboration with A02 we will analyze metabolic features of organoids in dependence of the tumor’s mechanoenvironment. In addition, for direct comparison of single cell and bulk tissue mechanical characterizations, we will be collaborating with B03 for using their MRE compatible bioreactor, as well as with C02 and C03 for technical support with tabletop mMRE experiments conducted in Dresden and with C01 for patient tissue mechanical data obtained in vivo. We expect from the integrated approach that is uniquely provided by this research unit not only a better understanding of the causes of tumor tissue scale mechanical changes, but also to establish more realistic organoids models that can be ultimately used as avatars for tailored treatment options.
DFG Programme
Research Units
