Rahmati Nahid, Maftoon Nima
Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada.
Centre for Bioengineering and Biotechnology, University of Waterloo, Waterloo, ON, Canada.
Front Bioeng Biotechnol. 2024 May 27;12:1393413. doi: 10.3389/fbioe.2024.1393413. eCollection 2024.
The dynamics of circulating tumor cells (CTCs) within blood vessels play a pivotal role in predicting metastatic spreading of cancer within the body. However, the limited understanding and method to quantitatively investigate the influence of vascular architecture on CTC dynamics hinders our ability to predict metastatic process effectively. To address this limitation, the present study was conducted to investigate the influence of blood vessel tortuosity on the behaviour of CTCs, focusing specifically on establishing methods and examining the role of shear stress in CTC-vessel wall interactions and its subsequent impact on metastasis. We computationally simulated CTC behaviour under various shear stress conditions induced by vessel tortuosity. Our computational model, based on the lattice Boltzmann method (LBM) and a coarse-grained spectrin-link membrane model, efficiently simulates blood plasma dynamics and CTC deformability. The model incorporates fluid-structure interactions and receptor-ligand interactions crucial for CTC adhesion using the immersed boundary method (IBM). Our findings reveal that uniform shear stress in straight vessels leads to predictable CTC-vessel interactions, whereas in curved vessels, asymmetrical flow patterns and altered shear stress create distinct adhesion dynamics, potentially influencing CTC extravasation. Quantitative analysis shows a 25% decrease in the wall shear stress in low-shear regions and a 58.5% increase in the high-shear region. We observed high-shear regions in curved vessels to be potential sites for increased CTC adhesion and extravasation, facilitated by elevated endothelial expression of adhesion molecules. This phenomenon correlates with the increased number of adhesion bonds, which rises to approximately 40 in high-shear regions, compared to around 12 for straight vessels and approximately 5-6 in low-shear regions. The findings also indicate an optimal cellular stiffness necessary for successful CTC extravasation in curved vessels. By the quantitative assessment of the risk of CTC extravasation as a function of vessel tortuosity, our study offers a novel tool for the prediction of metastasis risk to support the development of personalized therapeutic interventions based on individual vascular characteristics and tumor cell properties.
血管内循环肿瘤细胞(CTC)的动态变化在预测癌症在体内的转移扩散中起着关键作用。然而,对血管结构对CTC动态影响的定量研究的理解和方法有限,这阻碍了我们有效预测转移过程的能力。为了解决这一局限性,本研究旨在探讨血管迂曲度对CTC行为的影响,特别关注建立方法并研究剪切应力在CTC与血管壁相互作用中的作用及其对转移的后续影响。我们通过计算模拟了在血管迂曲度引起的各种剪切应力条件下CTC的行为。我们基于格子玻尔兹曼方法(LBM)和粗粒化血影蛋白连接膜模型的计算模型,有效地模拟了血浆动力学和CTC的变形能力。该模型使用浸入边界法(IBM)纳入了对CTC粘附至关重要的流固相互作用和受体-配体相互作用。我们的研究结果表明,直血管中的均匀剪切应力导致可预测的CTC与血管的相互作用,而在弯曲血管中,不对称的流动模式和改变的剪切应力产生了独特的粘附动力学,并可能影响CTC的外渗。定量分析表明,低剪切区域的壁面剪切应力降低了25%,高剪切区域增加了58.5%。我们观察到弯曲血管中的高剪切区域是CTC粘附和外渗增加的潜在部位,这是由粘附分子在内皮细胞上的表达升高所促进的。这种现象与粘附键数量的增加相关,在高剪切区域增加到约40个,而直血管约为12个,低剪切区域约为5-6个。研究结果还表明,弯曲血管中成功的CTC外渗需要最佳的细胞硬度。通过将CTC外渗风险作为血管迂曲度的函数进行定量评估,我们的研究提供了一种预测转移风险的新工具,以支持基于个体血管特征和肿瘤细胞特性的个性化治疗干预的开发。
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