Nanomechanical aspects of brain metastasis formation and amyotrophic lateral sclerosis
Résumé
Atomic force microscopy-based nanomechanical methods were directly applied in order to elucidate important questions related to brain metastasis formation and amyotrophic lateral sclerosis (ALS). Force mapping with single cell force spectroscopy was combined in order to gain direct insight into the surface “screening” process of tumor cells during their extravasation into the brain parenchyma. Furthermore, comparative SCFS measurements were performed between three melanoma cell types (WM35, A2058 and A375), showing altered invasive characteristics, and blood vessel lining endothelials in order to examine how the metastatic potential relates to tumor cell’s autonomous and inter-cellular nanomechanical properties. In case of ALS by comparing the adhesion of CD8+ cytotoxic T cells isolated from wild-type as well as SOD1G93A mutant mice against wild-type motor neurons we found that cytotoxic T cells are active contributors of neurodegeneration in the development of ALS. In addition, nanomechanical mapping of wild-type and SOD1G93A mutant mice derived single elongated myoblasts and multinuclear myotubes revealed differences in elasticity during early differentiation stage into myotubes. These findings provide valuable knowledge to the understanding of brain metastasis formation and ALS pathogenesis.