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Constructing proper in vitro tumor immune microenvironment (TIME) is important for cancer immune‐therapy studies, while the selection of biomaterials is critical. As innate immune cells, macrophages can target and kill cancer cells in vivo at the early stage of tumor development. However, this targeting phenomenon has not been observed in vitro. Herein, a quasi‐3D in vitro cell culture model is constructed to mimic TIME by integrating hydrogel collagen as extracellular matrix for cells. In the collagen‐based quasi‐3D in vitro system, for the first time, it is found that macrophages can be attracted toward cancer cells along the dynamically reconstructed collagen fibers. By combining traction force microscopy and customized micro‐manipulator system, it is revealed that the collagen matrix‐transmitted tensile force signaling precisely guides the migration of macrophages toward cancer cells. The mechano‐responsiveness mechanism is related to the activation of mechanosensitive ion channels, and the induced local increase of calcium signal, which is proved to enhance the F‐actin assembly and to guide the cell migration. This novel mechanism advances the understanding of the role of collagen fibers in mechanotaxis of macrophages. Taken together, it has great potential for assisting biomaterial designs in developing new drug‐screening models and clinical strategies for cancer immune‐therapy. [ABSTRACT FROM AUTHOR]

Synapse formation in complex neuronal network is a pivotal process for normal functioning of nervous system. Although intense research has been conducted, how neurons and axons are guided toward the target remains largely unclear. In traditional opinions, axons are directed through chemotaxis, while recently mechanotaxis has been brought up as a potential complementary mechanism, as it can provide delicately controlled signals in addition to the random diffusive chemical cues. To further explore the path‐finding mechanism, a quasi‐3D in vitro model for neuronal cells is constructed by integrating hydrogel collagen I as extracellular matrix (ECM), and primary mouse cortical neurons and PC12 cells are tested. It is strikingly found out that axons and neuronal cells can be precisely guided toward target neurites via ECM. By developing a label‐free traction force microscopy technique, the force networks among neurons are presented, validating that the fibrous matrix‐transmitted paratensile signals can assist the axon pathfinding. This precise axon guidance is related to the activation of mechanosensitive ion channels, calcium signaling, and probably the following F‐actin assembly. This mechanism can potentially assist developing clinical applications and designing biomaterials in near future. [ABSTRACT FROM AUTHOR]

This precise axon guidance mechanism is associated with the activation of mechanosensitive ion channels, calcium signals, and subsequent F-actin assembly. Axon pathfinding, extracellular matrix, mechanical signals, synapse formation Keywords: axon pathfinding; extracellular matrix; mechanical signals; synapse formation EN axon pathfinding extracellular matrix mechanical signals synapse formation 1 1 1 09/07/23 20230905 NES 230905 B Axon Pathfinding b In article number 2301926, Qihui Fan, Fangfu Ye, and co-workers show that the mechanical signals transmitted through the fibrous extracellular matrix enable precise guidance of axons and neuronal cells towards target neurites, leading to highly efficient neural network formation. [Extracted from the article]