Anna Taubenberger: Mapping cell volume and mechanical changes within tumor spheroids under confinement

Vortragender/Speaker: Dr. Anna Taubenberger (TU Dresden, Center for Molecular and Cellular Bioengineering - CMCB)
Ansprechpartner/Contact: Jun. Prof. Dr. Markus Schmidtchen
Videostream (BBB): (on request)

Titel/Title:
Mapping cell volume and mechanical changes within tumor spheroids under confinement

Zusammenfassung/Abstract:
Tumor tissues are mechanically altered across multiple spatial scales, from the subcellular to the tissue level, and these changes contribute to cancer progression. Effects of mechanically altered microenvironments on tumor cells are well studied in a systematic manner using bioengineered 3D in vitro models. Previous studies indicate that tumor spheroids adapt their growth and mechanical properties when grown in confining 3D microenvironments. Still, the temporal dynamics and molecular basis of this mechanical adaption remain poorly understood. Here we cultured tumor spheroids grown from single cancer cells in mechanically well-defined biohybrid ECM mimicking hydrogels. Growth in stiffened hydrogels was associated with changes in cell morphology, gene expression, and spheroid growth. Brillouin microscopy in-situ mapping revealed that cells tumor spheroids altered their mechanical properties under confinement and when acquiring invasive traits. Within few days, transitions from single cells to multicellular structures were associated with drastic cell volume decreases and higher Brillouin frequency shifts. Drugs interfering with cell-cell junctions and intermediate filaments but not F-actin filaments nor microtubules affected the mechanical phenotype of cells measured by Brillouin microscopy. Taken together, our study provides insights into how tumor cells adapt their volumes and mechanical properties to microenvironment stiffness and confinement and when forming multicellular and invasive structures, which are relevant aspects in tumorigenesis and tumor progression.