Porous hydrogel scaffolds are ideal candidates for mimicking cellular microenvironments, regarding both structural and mechanical aspects. We present a novel strategy to use uniquely designed ceramic networks as templates for generating hydrogels with a network of interconnected pores in the form of microchannels. The advantages of this new approach are the high and guaranteed interconnectivity of the microchannels, as well as the possibility to produce channels with diameters smaller than 7 μm. Neither of these assets can be ensured with other established techniques. Experiments using the polyacrylamide substrates produced with our approach have shown that the migration of human pathogenic Acanthamoeba castellanii trophozoites is manipulated by the microchannel structure in the hydrogels. The parasites can even be captured inside the microchannel network and removed from their incubation medium by the porous polyacrylamide, indicating the huge potential of our new technique for medical, pharmaceutical, and tissue engineering applications.
In many situations, cells migrate through tiny orifices. Examples include the extravasation of immune cells from the bloodstream for fighting infections, the infiltration of cancer cells during metastasis, and the migration of human pathogens. An extremely motile and medically relevant type of human pathogen is Acanthamoeba castellanii. In the study presented here, we investigated how a combination of microparticles and microstructured interfaces controls the migration of A. castellanii trophozoites. The microinterfaces comprised well-defined micropillar arrays, and the trophozoites easily migrated through the given constrictions by adapting the shape and size of their intracellular vacuoles and by adapting intracellular motion. After feeding the trophozoite cells in microinterfaces with synthetic, stiff microparticles of various sizes and shapes, their behavior changed drastically: if the particles were smaller than the micropillar gap, migration was still possible. If the cells incorporated particles larger than the pillar gap, they could become immobilized but could also display remarkable problem-solving capabilities. For example, they turned rod-shaped microparticles such that their short axis fit through the pillar gap or they transported the particles above the structure. As migration is a crucial contribution to A. castellanii pathogenicity and is also relevant to other biological processes in microenvironments, such as cancer metastasis, our results provide an interesting strategy for controlling the migration of cells containing intracellular particles by microstructured interfaces that serve as migration-limiting environments.
Strain‐stiffening, i.e. the nonlinear stiffening of a material in response to a strain, is an intrinsic feature of many biological systems, including skin, blood vessels, and single cells. To avoid a mismatch in mechanical properties, synthetic materials in contact with such biological systems should also be strain‐stiffening. Conventional strain‐stiffening materials are either highly dependent on the applied strain‐rate, or only available for a limited stiffness regime. Both aspects limit the applicability of these materials. In contrast, living cells employ a dynamic strain‐stiffening mechanism that is based on the cross‐linking of cytoskeletal fibers in response to external stress. This strain‐stiffening of the cytoskeleton is mimicked in a mechanical metamaterial by a minimalistic structure consisting of parallel slats connected to backbones. Herein, it is demonstrated experimentally that the structures can be adapted such that the strain required for stiffening, the final stiffness, as well as the degree of stiffening can be tuned, particularly by combining several strain‐stiffening elements. These properties make the structure promising for the development of devices that should resemble the mechanical properties of human soft tissues, e.g., skin‐integrated flexible electronics and blood vessel grafts.
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