Biological Physics Division, Peter Debye Institute of Soft Matter Physics, Faculty of Physics and Earth Science, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany.
Cells. 2024 Jan 2;13(1):96. doi: 10.3390/cells13010096.
Extracellular biophysical properties have particular implications for a wide spectrum of cellular behaviors and functions, including growth, motility, differentiation, apoptosis, gene expression, cell-matrix and cell-cell adhesion, and signal transduction including mechanotransduction. Cells not only react to unambiguously mechanical cues from the extracellular matrix (ECM), but can occasionally manipulate the mechanical features of the matrix in parallel with biological characteristics, thus interfering with downstream matrix-based cues in both physiological and pathological processes. Bidirectional interactions between cells and (bio)materials in vitro can alter cell phenotype and mechanotransduction, as well as ECM structure, intentionally or unintentionally. Interactions between cell and matrix mechanics in vivo are of particular importance in a variety of diseases, including primarily cancer. Stiffness values between normal and cancerous tissue can range between 500 Pa (soft) and 48 kPa (stiff), respectively. Even the shear flow can increase from 0.1-1 dyn/cm (normal tissue) to 1-10 dyn/cm (cancerous tissue). There are currently many new areas of activity in tumor research on various biological length scales, which are highlighted in this review. Moreover, the complexity of interactions between ECM and cancer cells is reduced to common features of different tumors and the characteristics are highlighted to identify the main pathways of interaction. This all contributes to the standardization of mechanotransduction models and approaches, which, ultimately, increases the understanding of the complex interaction. Finally, both the in vitro and in vivo effects of this mechanics-biology pairing have key insights and implications for clinical practice in tumor treatment and, consequently, clinical translation.
细胞外的生物物理特性对广泛的细胞行为和功能具有特殊意义，包括生长、运动、分化、凋亡、基因表达、细胞-基质和细胞-细胞黏附以及信号转导，包括力学转导。细胞不仅对细胞外基质（ECM）中明确的机械信号做出反应，而且偶尔可以与生物特性平行地操纵基质的机械特性，从而干扰生理和病理过程中基于基质的下游信号。细胞与体外（生物）材料之间的双向相互作用可以改变细胞表型和力学转导，以及 ECM 结构，无论是有意还是无意。细胞与基质力学在体内的相互作用在多种疾病中都非常重要，包括主要的癌症。正常组织和癌变组织之间的硬度值分别在 500 Pa（软）到 48 kPa（硬）之间。即使剪切流也可以从 0.1-1 dyn/cm（正常组织）增加到 1-10 dyn/cm（癌变组织）。目前，在各种生物长度尺度上的肿瘤研究中有许多新的活动领域，本综述强调了这些领域。此外，将 ECM 和癌细胞之间相互作用的复杂性简化为不同肿瘤的共同特征，并突出了这些特征以识别主要的相互作用途径。所有这些都有助于力学转导模型和方法的标准化，最终增加对复杂相互作用的理解。最后，这种力学-生物学配对的体外和体内作用对肿瘤治疗的临床实践具有关键的见解和影响，从而促进了临床转化。
