RESUMO
Cancer progression is associated with alternations in the cytoskeletal architecture of cells and, consequently, their mechanical properties such as stiffness. Changing the mechanics of cells enables cancer cells to migrate and invade to distant organ sites. This process, metastasis, is the main reason for cancer-related mortality. Cell migration is an essential step towards increasing the invasive potential of cells. Although many studies have shown that the migratory speed and the invasion of cells can be inversely correlated to the stiffness of cells, some other investigations indicate opposing results. In the current work, based on the strain energy stored in cells due to the contractile forces, we defined an energy-dependent term, migratory index, to approximate how changes in the mechanical properties of cells influence cell migration required for cancer progression. Cell migration involves both cell deformation and force transmission within cells. The effects of these two parameters can be represented equally by the migratory index. Our mechanical modelling and computational study show that cells depending on their shape, size and other physical parameters have a maximum migratory index taking place at a specific range of cell bulk elasticity, indicating the most favourable conditions for invasive mobility. This approximate model could be used to explain why the stiffness of cells varies during cancer progression. We believe that the stiffness of cancer or malignant cells depending on the stiffness of their normal or non-malignant counterparts is either decreased or increased to reach the critical condition in which the mobility potential of cells is approximated to be maximum.
RESUMO
In the ancient traditional Indian Ayurvedic system of natural healing, gold nanoparticles (Swarna Bhasma, gold ash) have been used for its therapeutic benefits as far back as 2500 B.C. Ayurvedic medicinal preparations are complex mixtures that include many plant-derived products and metals. Bhasmas date as far back as the 8th century and are made by samskaras (processings), such as shodhana (purification and potentiation), jarana (roasting), and marana (incineration, trituration) in the presence of plant products, including juices and concoctions. Previous studies characterized the physical properties of gold ash, and the mechanisms of its entry into human cells, but only preliminary data exist on its toxicity. Before using nanoparticles for therapeutic application, it is extremely important to study their toxicity and cellular internalization. In the present study, various imaging techniques were used to investigate Swarna Bhasma's (gold nanopowder) toxicity in both cancerous and noncancerous cells (HeLa and HFF-1) and to characterize its spectral properties. The results showed that gold ash particles had no impact on the cellular viability of both HeLa and HFF-1 cells, even at high concentrations or long incubation times. Moreover, it was found that the internalization level of Swarna Bhasma to cells may be improved by mechanical breaking of the large aggregates into smaller agglomerates. Hyperspectral images revealed that after breaking, the small agglomerates have different spectral properties in cells, compared to the original aggregates, suggesting that size of particles is instrumental for the subcellular interaction with human cells.
