ABSTRACT
Faculty of Physics and Earth Science, Institute of Experimental Physics I, Soft Matter Physics Division, University of Leipzig, Linnéstr. 5, 04103 Leipzig, Germany. Email: claudia.mierke@t-online.de
The malignancy of the cancer disease depends mainly on the size of the primary tumor, its location, and the capability of single or clustered cancer cells to spread from the primary tumor, invade into the surroundings and fi nally to metastasize, which is indicated by the formation of secondary tumors in targeted organs. This process of metastasis formation has long been seen as a variety of genetic alterations that had occurred during the progression of cancer disease. The focus of molecular and cellular biological research was on the investigation of numerous mutants that showed altered cell motility in artifi cial extracellular matrices. The fi rst motility assays have been performed on pure plastic or glass substrates, and they have been further improved to assays using thin layers of extracellular matrix (ECM) proteins as a surface-coating on top of the planar substrates. Then, motility of cells through a mesh of defi ned “undeformable” stabile pores (named transwell assays or Boyden Chamber assays) has been studied. As these artifi cial in vitro matrices are still far away from mimicking in vivo ECMs or connective tissue perfectly, they are still useful to investigate the mechanical properties, which are adjustable within these ECMs to obtain the mechanical properties of different tissue types. These in two dimensions performed motility assays have been further developed by using three-dimensional (3D) ECMs, which contain mainly collagen fi bers or matrigel constituents (ECM extracted from tumor lesions) and have ‘‘deformable or bendable’’ pores with adjustable size suitable for each cell type studied. These artifi cial in vitro ECMs are still far away from rebuilding in vivo ECMs or connective
tissue, but they are a useful tool to investigate the mechanical properties of the cell’s surroundings, which are adjustable within these ECMs over a wide range to mimic the mechanical properties of different tissue types or even the enhanced stiffness of tumor tissue. Unfortunately, the mechanical properties of these ECM substrates have over a long time period been simply ignored. Moreover, even the mechanical properties of migratory cells or cells, which represent a barrier for migratory cells such as endothelial cells building the inner lining of blood or lymph vessels have not been studied. In the last few years, the mechanical properties of the (cancer) cells have become the focus of recent research studies (Zaman et al. 2006, Mierke et al. 2008a, Fritsch et al. 2010, Yu et al. 2011, Mierke et al. 2011a, Guck et al. 2005). Several studies analyzed (cancer) cells in connective tissue where they are exposed to forces such as protrusive forces, contractile forces, compressive forces, tensile forces, shear forces of the vessel stream (Ingber 2006, Paszek et al. 2009, Weaver et al. 2002). These forces fulfi ll prominent functions in cellular and tissue shaping, organ development as well as in maintenance and homeostasis of the tissue (Paszek et al. 2005, DuFort et al. 2011). The focus of these studies was on how (cancer) cells sense and respond to these forces, which seems to be set by the biomechanical properties of the (cancer) cells, their adjacent cells and the ECM (Ingber 2006, Paszek et al. 2009, Du Fort et al. 2011, Miteva et al. 2010). In a recent study, the mechanical properties of human endothelial cells have been investigated (Mierke 2011a). In more detail, alterations of endothelial mechanical properties by certain breast, bladder and kidney cancer cells have been observed (Mierke 2011a). Additionally the mechanical properties of the ECM and ECM-embedded cells such as endothelial cells play a prominent role in malignant cancer progression. As the surrounding tissue of neoplasms and tumors is altered in terms of the mechanical properties compared to ‘‘normal’’ tissue of healthy species, the mechanical properties of cancer cells such as the stiffness (the inverse of the compliance) and contractile forces may also be affected and become the focus of biophysical research groups.
