Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance.

Cell motility is central to tissue homeostasis in health and disease, and there is hardly any cell in the body that is not motile at a given point in its life cycle. Important physiological processes intimately related to the ability of the respective cells to migrate include embryogenesis, immune defense, angiogenesis, and wound healing. On the other side, migration is associated with life-threatening pathologies such as tumor metastases and atherosclerosis. Research from the last ≈ 15 years revealed that ion channels and transporters are indispensable components of the cellular migration apparatus. After presenting general principles by which transport proteins affect cell migration, we will discuss systematically the role of channels and transporters involved in cell migration.

Cell movement-for example, during embryogenesis or tumor metastasis-is a complex dynamical process resulting from an intricate interplay of multiple components of the cellular migration machinery. At first sight, the paths of migrating cells resemble those of thermally driven Brownian particles. However, cell migration is an active biological process putting a characterization in terms of normal Brownian motion into question. By analyzing the trajectories of wild-type and mutated epithelial (transformed Madin-Darby canine kidney) cells, we show experimentally that anomalous dynamics characterizes cell migration. A superdiffusive increase of the mean squared displacement, non-Gaussian spatial probability distributions, and power-law decays of the velocity autocorrelations is the basis for this interpretation. Almost all results can be explained with a fractional Klein-Kramers equation allowing the quantitative classification of cell migration by a few parameters. Thereby, it discloses the influence and relative importance of individual components of the cellular migration apparatus to the behavior of the cell as a whole. data analysis ͉ fractional dynamics ͉ non-Brownian motion N early all cells in the human body are mobile at a given time during their life cycle. Embryogenesis, wound-healing, immune defense, and the formation of tumor metastases are well known phenomena that rely on cell migration. Extensive experimental work revealed a precise spatial and temporal coordination of multiple components of the cellular migration machinery such as the actin cytoskeleton, cell-substrate and cell-cell interactions, and the activity of ion channels and transporters (1-4). These findings are the basis for detailed molecular models representing different microscopic aspects of the process of cell migration such as the protrusion of the leading edge of the lamellipodium, or actin dynamics (5). Mathematical continuum models, in contrast, focus on collective properties of the entire cell to explain requirements for the onset of motion and some typical features of cell motility (6). These models are usually limited to small spatiotemporal scales. Therefore, they provide little information about how the integration of protrusion of the lamellipodium, retraction of the rear part, and force transduction onto the extracellular matrix lead to the sustained long-term movement of the entire cell. This process is characterized by alternating phases of directed migration, changes of direction, and polarization. The coordinated interaction of these phases suggests the existence of intermittency (7) and of strong spatiotemporal correlations. It is therefore an important question whether the long-term movement of the entire cell can still be understood as a simple diffusive behavior like usual Brownian motion (8, 9) or whether more advanced concepts of dynamic modeling have to be applied (10, 11). Results and DiscussionWe performed migration experiments and analyzed the trajectories of two migrating transformed renal epithelial MadinDar...

Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration during embryonic development and a chemoattractant during postnatal migratory responses including wound healing. We previously showed that PDGFRα signaling is coordinated by the primary cilium in quiescent cells. However, little is known about the function of the primary cilium in cell migration. Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88^Tg737Rpw) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA is absent, leading to unregulated high speed and uncontrolled directional cell displacement during wound closure, with subsequent defects in wound healing. These data suggest that in coordination with cytoskeletal reorganization, the fibroblast primary cilium functions via ciliary PDGFRα signaling to monitor directional movement during wound healing.

Cancer accounts for 13% of the yearly total mortality worldwide. Most cancer deaths are the sequel of metastatic diseases rather than of primary tumor growth. Thus, the major challenge in tumor therapy is the tumor cells' ability to metastasize. The extent to which a tumor metastasizes correlates with the tumor cells' migratory activity. Tumor cell migration requires a coordinated formation and release of cell adhesion contacts, a controlled cytoskeletal dynamics, the digestion and reorganization of the extracellular matrix, and local ion and water transport across the plasma membrane. All of these operations depend on intracellular pH (pH(i)) and extracellular pH (pH(e)). Numerous H(+), HCO (3) (-) , and monocarboxylate transporters as well as different carbonic anhydrase isozymes have considerable impact on pH(i) and pH(e) which spotlights them as possible, potential targets for anticancer therapeutics. Especially in solid tumors whose vascularization is often not sufficient, tumor cells cope with hypoxia and the resulting glycolysis by overexpressing the Na(+)/H(+) exchanger NHE1, monocarboxylate transporters MCT1 and/or MCT4, and the carbonic anhydrase CA IX. NHE1, MCT, and CA IX activity lead to an acidification of the extracellular space in order to maintain the cytosolic pH homeostasis stable. The present article gives a review on how this characteristic, acidic tumor micro- and nanoenvironment controls tumor cell migration.