粘弹性
消散
机制(生物学)
肿瘤进展
材料科学
癌症
肿瘤微环境
生物物理学
癌症研究
生物
肿瘤细胞
物理
复合材料
遗传学
量子力学
热力学
作者
Muhamed Hadzipasic,Sue Zhang,Zhuoying Huang,Rachel Passaro,M.S. Sten,Ganesh M. Shankar,Hadi T. Nia
出处
期刊:Biomaterials
[Elsevier]
日期:2024-03-01
卷期号:305: 122431-122431
被引量:1
标识
DOI:10.1016/j.biomaterials.2023.122431
摘要
Tumors are complex materials whose physical properties dictate growth and treatment outcomes. Recent evidence suggests time-dependent physical properties, such as viscoelasticity, are crucial, distinct mechanical regulators of cancer progression and malignancy, yet the genesis and consequences of tumor viscoelasticity are poorly understood. Here, using Wide-bandwidth AFM-based ViscoElastic Spectroscopy (WAVES) coupled with mathematical modeling, we probe the origins of tumor viscoelasticity. From single carcinoma cells to increasingly sized carcinoma spheroids to established tumors, we describe a stepwise evolution of dynamic mechanical properties that create a nanorheological signature of established tumors: increased stiffness, decreased rate-dependent stiffening, and reduced energy dissipation. We dissect this evolution of viscoelasticity by scale, and show established tumors use fluid-solid interactions as the dominant mechanism of mechanical energy dissipation as opposed to fluid-independent intrinsic viscoelasticity. Additionally, we demonstrate the energy dissipation mechanism in spheroids and established tumors is negatively correlated with the cellular density, and this relationship strongly depends on an intact actin cytoskeleton. These findings define an emergent and targetable signature of the physical tumor microenvironment, with potential for deeper understanding of tumor pathophysiology and treatment strategies.
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