Cancer cells optimize elasticity for efficient migration

Abstract

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.

Cancer-Nano-Interaction: From Cellular Uptake to Mechanobiological Responses

“…Mechanobiology describes how cell mechanics and mechanical forces influence cell behavior, cell morphogenesis, and diseases such as cancer [23,73]. In the context of mechanobiology, the mechanical properties of cells play significant roles in sensing and responding to their external surrounding [25,[73][74][75]. With the help of the cytoskeleton, cells can resist the deformation induced by their microenvironment and alter their shapes during movement by polymerizing or fluidizing the polymeric structure of the cytoskeleton [76][77][78].…”

“…The cytoskeleton structure (cell mechanics) plays a central role in controlling cellular functions, and any abnormal changes may cause dysfunctions. For example, during cancer, the elasticity (stiffness) of cells is decreased, enabling them to invade other organs and metastasize [25,79]. In NBI, where NPs interact with cellular organelles and cytoskeletal structures, they might influence cell mechanobiology and, in return, alter cellular responses such as cell migration, cell adhesion, and cancer metastasis.…”

“…Various techniques can be implemented to measure the mechanobiological properties of single cells, such as viscosity and elasticity. The elastic modulus and viscosity modulus are typically used to express the mechanical properties of cells [25,88]. In the elastic modulus, the applied forces are related to cell deformation, while in the viscosity, time-dependent stress relaxation is measured in response to a step displacement [21,96].…”

“…In the NBI field, researchers have long studied physiochemical properties of NPs and their effects on cellular uptake, cytotoxicity, and intracellular fate [19,20], while few researchers have addressed NPs' exposure effects on cell mechanics and biological activities (Figure 1). The mechanobiological properties such as stiffness play an important role in modulating the cellular behavior, and any abnormal changes could cause cellular dysfunctions such as impaired migration, impaired differentiation, and impaired wound healing [21][22][23][24][25]. For example, during cancer progression, the stiffness of cells is reduced, giving a high ability of migration and invasion [21,25].…”

“…The mechanobiological properties such as stiffness play an important role in modulating the cellular behavior, and any abnormal changes could cause cellular dysfunctions such as impaired migration, impaired differentiation, and impaired wound healing [21][22][23][24][25]. For example, during cancer progression, the stiffness of cells is reduced, giving a high ability of migration and invasion [21,25]. Mechanobiological measurements provide valuable information on cell functionality and health [26].…”