Anomalous diffusion of particles in living breast cancer cells – an indication to cancer-specific function

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Daphne Weihs
31/12/2014 - 10:30
Colloquium Room

Mechanics of cancer cells are directly linked to their metastatic potential (MP), or ability to produce a secondary tumor at a distant site. Metastatic cells can squeeze through blood vessel walls and tissue. Such considerable structural changes rely on rapid remodeling of internal cell structure and mechanics. We perform a comparative study, using particle-tracking to evaluate the intracellular mechanics of living epithelial breast cells with varying invasiveness. Probe-particle transport differs between the cell types, likely relating to their cytoskeleton network-structure and underlying transport. The basic analysis included evaluation of the time-dependent mean square displacement (MSD), the second power of the displacement. Particles in all the evaluated cell lines exhibit anomalous super-diffusion with an MSD scaling exponent of 1.4, at short lag times below 1 second. While indicating active transport within the cells, the MSD alone cannot reveal the underlying mechanisms. Hence, we analyze particle motion through a combination the MSD, other powers of the displacement, and various trajectory and displacement analysis procedures to identify structural and dynamic changes associated with metastatic capabilities of cells.

The dynamic cytoskeleton and especially the molecular motors acting on it provide the cell with its remodeling capabilities and allow active transport within the cell. While active transport in living cells has been well-documented, the underlying mechanisms have not been determined. Here, we systematically target the cytoskeleton, molecular motors, and ATP energy related processes to determine their roles in particle transport. Our results show that particle motion is likely driven by different processes in each cell type. Intracellular transport in high MP cells is suggested to originate from fluctuations of microtubule filaments as well as from direct and indirect interactions between particles and microtubule-associated molecular motors. In the low MP cells we suggest that motion results from direct and indirect interactions between particles and microtubule-associated molecular motors, being transported by them or nudged by passing motors, respectively. The benign cells, however, reveal significant involvement of the acto-myosin network, where particle motion was related to network contractions. Thus, we are able to provide insight into dynamic intracellular structure and mechanics that can support the unique function and invasive capabilities of highly metastatic cells.