Institute for Drug Research, Faculty of Medicine ,the Hebrew University of Jerusalem, Jerusalem
Abstract:
Cancer cells are mechanically distinguishable from normal cells. The malignancy potential is correlated with the ability of cells to perform elastic and dynamic shape modulations, and to adjust to different mechanical environments. The talk will outline theoretical and experimental studies of cancer mechanics preformed in our lab and their potential in clinical applications. In a comprehensive research we found a triangular correlation between cell deformability, cancer aggressiveness and the cell ability to uptake nano / micro particles. Using thermodynamic models we have shown that during particle absorbance, the distortions of the 3D cytoskeleton and of the 2D cell membrane largely depend on the size, shape and rigidity of the particles. Therefore, tuning the physical properties of particles can control their specific uptake by cancer vs normal cells. Accordingly, we introduced the concept of mechanical based cancer specificity, where adjustment of the physical properties of drug carriers enhances their specific interaction with cancer cells, whereby reducing the challenging need of molecular targets.
We verified our theoretical predictions using a wide span of experimental schemes, including flowcytometry, AFM force spectroscopy, various types of microscopy (followed by our image analysis) and functional tests of cell invasiveness and malignancy. The triangular correlation was demonstrated in several types of cancer cells, and also in sub – populations of cells that we sorted based on their phagocytic capacity. In addition, we developed dynamical theories for the quantification of tissue / cell elastic moduli based on indentation and compression experiments. Our comprehensive studies verified the high relevance of mechanical aspects in cancer research and their potential contribution to the design of drug carriers and to diagnostics.