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Although integrins are responsible for the interaction of cells with their environment, e.g., the extracellular matrix or artificial substrates, there is still a lack of knowledge about their role in cell adhesion and migration on protein-coated substrates with microtopography. Understanding such interactions could lead to new applications in e.g., medical implants as well as shed light on processes such as embryonic development, angiogenesis, wound healing, and tumor progression. In this work, the influence of surface topography and chemistry on αvβ3 and α5β1 integrin-mediated cell adhesion and migration of healthy and malignant human cell types (human coronary artery endothelial cells, human osteosarcoma cells, and human skin fibroblasts cells) was studied, using microgrooved and flat substrates covered by two different extracellular proteins, fibronectin and vitronectin. Although some general behaviors can be observed, cell migration (speed, directionality, and persistence time) and morphological adaptation (cell area, aspect ratio, and circularity) of cells on protein coated microgrooved substrates are mainly dependent on the cell type and its specific integrin expression.
Endogenous electrical fields play an important role in various physiological and pathological events. Yet the effects of electrical cues on processes such as wound healing, tumor development or metastasis are still rarely investigated, though it is known that direct current electrical fields can alter cell migration or proliferation in vitro. Several 2D experimental models for studying cell responses to direct current electrical fields have been presented and characterized but suitable experimental models for electrotaxis studies in 3D are rare. Here we present a novel, easy-to-produce, multi-well-based galvanotactic-chamber for the use in 2D and 3D cell experiments for investigations on the influence of electrical fields on tumor cell migration and tumor spheroid growth. Our presented system allows the simultaneous application of electrical field to cells in four chambers, either cultured on the bottom of the culture-plate (2D) or embedded in hydrogel filled channels(3D). The set-up is also suitable for, live-cell-imaging. Validation tests show stable electrical fields and high cell viabilities inside the channel. Tumor spheroids of various diameters can be exposed to direct current electrical fields up to one week.
Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear leukocyte (PMN), are the first cells to be activated during inflammation and subsequently migrate toward an injured tissue or infection site. This response is dependent on both biochemical signaling and the extracellular environment, one aspect of which includes increased temperature in the tissues surrounding the inflammation site. In our study, we analyzed temperature-dependent neutrophil migration using differentiated HL-60 cells. The migration speed of differentiated HL-60 cells was found to correlate positively with temperature from 30 to 42 °C, with higher temperatures inducing a concomitant increase in cell detachment. The migration persistence time of differentiated HL-60 cells was higher at lower temperatures (30–33 °C), while the migration persistence length stayed constant throughout the temperature range. Coupled with the increased speed observed at high temperatures, this suggests that neutrophils are primed to migrate more effectively at the elevated temperatures characteristic of inflammation. Temperature gradients exist on both cell and tissue scales. Taking this into consideration, we also investigated the ability of differentiated HL-60 cells to sense and react to the presence of temperature gradients, a process known as thermotaxis. Using a two-dimensional temperature gradient chamber with a range of 27–43 °C, we observed a migration bias parallel to the gradient, resulting in both positive and negative thermotaxis. To better mimic the extracellular matrix (ECM) environment in vivo, a three-dimensional collagen temperature gradient chamber was constructed, allowing observation of biased neutrophil-like differentiated HL-60 migration toward the heat source.
T cell migration plays an essential role in the immune response and T cell-based therapies. It can be modulated by chemical and physical cues such as electric fields (EFs). The mechanisms underlying electrotaxis (cell migration manipulated by EFs) are not fully understood and systematic studies with immune cells are rare. In this in vitro study, we show that direct current EFs with strengths of physiologically occurring EFs (25–200 mV/mm) can guide the migration of primary human CD4+ and CD8+ T cells on 2D substrates toward the anode and in a 3D environment differentially (CD4+ T cells show cathodal and CD8+ T cells show anodal electrotaxis). Overall, we find that EFs present a potent stimulus to direct T cell migration in different microenvironments in a cell-type-, substrate-, and voltage-dependent manner, while not significantly influencing T cell differentiation or viability.
