细胞外基质（ECM）的力学性质通过机械转导，调节细胞的分化、迁移和增殖等重要的行为。细胞-ECM机械转导的研究主要关注在2D培养体系中，即在一系列弹性底物上培养的细胞上。然而，在3D情境下，细胞经常在活体内与ECM相互作用，3D中细胞-ECM相互作用和机械转导机制与2D中可能不同。ECM表现出多种结构特征以及复杂的力学性质。在3D中，周围ECM的力学限制限制了细胞体积和细胞形状的变化，但使细胞通过延伸突起和调节细胞体积以及基于肌动蛋白的收缩能够对基质产生力。此外，细胞与基质的相互作用是动态的，因为基质不断重塑。因此，ECM的硬度、粘弹性和可降解性通常在调节3D中的细胞行为中起关键作用。3D机械转导的机制包括传统的整合素介导的途径，感知机械性质和最近描述的感应3D限制的机械敏感离子通道介导的途径，这两种途径聚合在细胞核，在下游调控转录和表型。机械转导涉及从发育到癌症的组织，并且越来越被利用于机械治疗。本文将讨论我们对3D中细胞-ECM机械转导的最新进展。© 2023. Springer Nature Limited.

Mechanical properties of extracellular matrices (ECMs) regulate essential cell behaviours, including differentiation, migration and proliferation, through mechanotransduction. Studies of cell-ECM mechanotransduction have largely focused on cells cultured in 2D, on top of elastic substrates with a range of stiffnesses. However, cells often interact with ECMs in vivo in a 3D context, and cell-ECM interactions and mechanisms of mechanotransduction in 3D can differ from those in 2D. The ECM exhibits various structural features as well as complex mechanical properties. In 3D, mechanical confinement by the surrounding ECM restricts changes in cell volume and cell shape but allows cells to generate force on the matrix by extending protrusions and regulating cell volume as well as through actomyosin-based contractility. Furthermore, cell-matrix interactions are dynamic owing to matrix remodelling. Accordingly, ECM stiffness, viscoelasticity and degradability often play a critical role in regulating cell behaviours in 3D. Mechanisms of 3D mechanotransduction include traditional integrin-mediated pathways that sense mechanical properties and more recently described mechanosensitive ion channel-mediated pathways that sense 3D confinement, with both converging on the nucleus for downstream control of transcription and phenotype. Mechanotransduction is involved in tissues from development to cancer and is being increasingly harnessed towards mechanotherapy. Here we discuss recent progress in our understanding of cell-ECM mechanotransduction in 3D.© 2023. Springer Nature Limited.