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The field of bioelectronics with the aim to contact cells, cell clusters, biological tissues and organoids has become a vast enterprise. Currently, it is mainly relying on classical micro‐ and nanofabrication methods to build devices and systems. Very recently the field is highly pushed by the development of novel printable organic, inorganic and biomaterials as well as advanced digital printing technologies such as laser and inkjet printing employed in this endeavor. Recent advantages in alternative additive manufacturing and 3D printing methods enable interesting new routes, in particular for applications requiring the incorporation of delicate biomaterials or creation of 3D scaffold structures that show a high potential for bioelectronics and building of hybrid bio‐/inorganic devices. Here the current state of printed 2D and 3D electronic structures and related lithography techniques for the interfacing of electronic devices with biological systems are reviewed. The focus lies on in vitro applications for interfacing single cell, cell clusters, and organoids. Challenges and future prospects are discussed for all‐printed hybrid bio/electronic systems targeting biomedical research, diagnostics, and health monitoring. [ABSTRACT FROM AUTHOR]

With the advent of mechanobiology, cell shape and forces have emerged as essential elements of cell behavior and fate, in addition to biochemical factors such as growth factors. Cell shape and forces are intrinsically linked to the physical properties of the environment. Extracellular stiffness guides migration of single cells and collectives as well as differentiation and developmental processes. In confined environments, cell division patterns are altered, cell death or extrusion might be initiated, and other modes of cell migration become possible. Tools from materials science such as adhesive micropatterning of soft elastic substrates or direct laser writing of 3D scaffolds have been established to control and quantify cell shape and forces in structured environments. Herein, a review is given on recent experimental and modeling advances in this field, which currently moves from single cells to cell collectives and tissue. A very exciting avenue is the combination of organoids with structured environments, because this will allow one to achieve organotypic function in a controlled setting well suited for long‐term and high‐throughput culture. [ABSTRACT FROM AUTHOR]

Cell behaviors significantly depend on the elastic properties of the microenvironments, which are distinct from commonly used polymer‐based substrates. Artificial elastic materials called metamaterials offer large freedom to adjust their effective elastic properties as experienced by cells, provided (i) the metamaterial unit cell is sufficiently small compared to the biological cell size and (ii) the metamaterial is sufficiently soft to deform by the active cell contraction. Thus, metamaterials targeting bio‐applications (bio‐metamaterials) appear as a promising path toward the mechanical control of stem cells. Herein, human mesenchymal stem cells (hMSCs) are cultured on three different types of planar periodic elastic metamaterials. To fulfill the above two key requirements, microstructured bio‐metamaterials have been designed and manufactured based on a silicon elastomer‐like photoresist and two‐photon laser printing. In addition to the conventional morphometric and immunocytochemical analysis, the traction force that hMSCs exert on metamaterials are inferred by converting the measured displacement‐vector fields into force‐vector fields. The differential responses of hMSCs, both on the cellular level and the sub‐cellular level, correlate with the calculated effective elastic properties of the bio‐metamaterials, suggesting the potential of bio‐metamaterials toward mechanical regulation of cell behaviors by the arrangement of unit cells. [ABSTRACT FROM AUTHOR]

Cell shape plays a fundamental role in many biological processes, including adhesion, migration, division and development, but it is not clear which shape model best predicts three-dimensional cell shape in structured environments. Here, we compare different modelling approaches with experimental data. The shapes of single mesenchymal cells cultured in custom-made 3D scaffolds were compared by a Fourier method with surfaces that minimize area under the given adhesion and volume constraints. For the minimized surface model, we found marked differences to the experimentally observed cell shapes, which necessitated the use of more advanced shape models. We used different variants of the cellular Potts model, which effectively includes both surface and bulk contributions. The simulations revealed that the Hamiltonian with linear area energy outperformed the elastic area constraint in accurately modelling the 3D shapes of cells in structured environments. Explicit modelling the nucleus did not improve the accuracy of the simulated cell shapes. Overall, our work identifies effective methods for accurately modelling cellular shapes in complex environments. Author summary: Cell shape and forces have emerged as important determinants of cell function and thus their prediction is essential to describe and control the behaviour of cells in complex environments. While there exist well-established models for the two-dimensional shape of cells on flat substrates, it is less clear how cell shape should be modeled in three dimensions. Different from the philosophy of the vertex model often used for epithelial sheets, we find that models based only on cortical tension as a constant geometrical surface tension are not sufficient to describe the shape of single cells in 3D. Therefore, we employ different variants of the cellular Potts model, where either a target area is prescribed by an elastic constraint or the area energy is described with a linear surface tension. By comparing the simulated shapes to experimental images of cells in 3D scaffolds, we can identify parameters that accurately model 3D cell shape. [ABSTRACT FROM AUTHOR]

S100A11 is a small Ca2+-activatable protein known to localize along stress fibers (SFs). Analyzing S100A11 localization in HeLa and U2OS cells further revealed S100A11 enrichment at focal adhesions (FAs). Strikingly, S100A11 levels at FAs increased sharply, yet transiently, just before FA disassembly. Elevating intracellular Ca2+ levels with ionomycin stimulated both S100A11 recruitment and subsequent FA disassembly. However, pre-incubation with the nonmuscle myosin II (NMII) inhibitor blebbistatin or with an inhibitor of the stretch-activatable Ca2+ channel Piezo1 suppressed S100A11 recruitment, implicating S100A11 in an actomyosin-driven FA recruitment mechanism involving Piezo1-dependent Ca2+ influx. Applying external forces on peripheral FAs likewise recruited S100A11 to FAs even if NMII activity was inhibited, corroborating the mechanosensitive recruitment mechanism of S100A11. However, extracellular Ca2+ and Piezo1 function were indispensable, indicating that NMII contraction forces act upstream of Piezo1-mediated Ca2+ influx, in turn leading to S100A11 activation and FA recruitment. S100A11-knockout cells display enlarged FAs and had delayed FA disassembly during cell membrane retraction, consistent with impaired FA turnover in these cells. Our results thus demonstrate a novel function for S100A11 in promoting actomyosin contractility-driven FA disassembly. [ABSTRACT FROM AUTHOR]