Dynamically Reconstructed Collagen Fibers for Transmitting Mechanical Signals to Assist Macrophages Tracing Breast Cancer Cells. (23rd December 2022)

• Record Type: Journal Article
• Authors: Yang, Chen; Wang, Xiaochen; Xie, Ruipei; Zhang, Yiyu; Xia, Tie; Lu, Ying; Ye, Fangfu; Zhang, Peipei; Cao, Ting; Xu, Ye; Fan, Qihui
• Is Part Of: Advanced functional materials. Volume 33:Number 9(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-23
• Subjects: cancer cells -- collagen fibers -- extracellular matrix -- macrophages -- mechanical signals; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202211807
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: 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 : As a major component of extracellular matrix (ECM) in vivo, collagen can assist transmission of mechanical signals, which will recruit macrophages toward cancer cells via activation of mechanosensitive ion channels. Complementary to chemotaxis, this novel ECM‐assisted mechanotaxis mechanism has great potential for cancer immunotherapy studies, such as providing effective in vitro models or new 3D drug‐screening platforms for drug development.