School of Engineering, Bernal Institute, University of Limerick, Limerick, Ireland.
Health Research Institute, University of Limerick, Limerick, Ireland.
Biomech Model Mechanobiol. 2017 Dec;16(6):2051-2062. doi: 10.1007/s10237-017-0937-z. Epub 2017 Jul 24.
Tumour metastasis in the lymphatics is a crucial step in the progression of breast cancer. The dynamics by which breast cancer cells (BCCs) travel in the lymphatics remains poorly understood. The goal of this work is to develop a model capable of predicting the shear stresses metastasising BCCs experience using numerical and experimental techniques. This paper models the fluidic transport of large particles ([Formula: see text] where [Formula: see text] is the particle diameter and W is the channel width) subjected to lymphatic flow conditions ([Formula: see text]), in a [Formula: see text] microchannel. The feasibility of using the dynamic fluid body interaction (DFBI) method to predict particle motion was assessed, and particle tracking experiments were performed. The experiments found that particle translational velocity decreased from the undisturbed fluid velocity with increasing particle size (5-14% velocity lag for [Formula: see text]). DFBI simulations were found to better predict particle behaviour than theoretical predictions; however, mesh restrictions in the near-wall region ([Formula: see text]) result in computationally expensive models. The simulations were in good agreement with the experiments ([Formula: see text] difference) across the channel ([Formula: see text]), with differences up to 25% in the near-wall region. Particles experience a range of shear stresses (0.002-0.12 Pa) and spatial shear gradients ([Formula: see text]) depending on their size and radial position. The predicted shear gradients are far in excess of values associated with BCC apoptosis ([Formula: see text]). Increasing our understanding of the shear stress magnitudes and gradients experienced by BCCs could be leveraged to elucidate whether a particular BCC size or location exists that encourages metastasis within the lymphatics.
肿瘤在淋巴管中的转移是乳腺癌进展的关键步骤。乳腺癌细胞（BCC）在淋巴管中迁移的动态过程仍知之甚少。这项工作的目标是开发一种能够使用数值和实验技术预测转移性 BCC 经历的剪切应力的模型。本文在[Formula: see text]微通道中，针对[Formula: see text]条件下（[Formula: see text]，其中[Formula: see text]是颗粒直径，W 是通道宽度）的淋巴流动条件，对大颗粒的流体输运进行建模。评估了使用动态流固相互作用（DFBI）方法预测颗粒运动的可行性，并进行了颗粒跟踪实验。实验发现，随着颗粒尺寸的增加（[Formula: see text]），颗粒的平移速度从无干扰的流体速度降低（[Formula: see text]）。DFBI 模拟比理论预测更能准确预测颗粒行为；然而，近壁区域的网格限制（[Formula: see text]）导致计算成本高昂的模型。模拟与实验在整个通道上（[Formula: see text]）非常吻合（[Formula: see text]），近壁区域的差异最大可达 25%。颗粒经历的剪切应力范围为（0.002-0.12 Pa）和空间剪切梯度（[Formula: see text]）取决于其尺寸和径向位置。预测的剪切梯度远远超过与 BCC 细胞凋亡相关的剪切梯度（[Formula: see text]）。增加我们对 BCC 经历的剪切应力幅度和梯度的理解，可以用来阐明是否存在特定的 BCC 尺寸或位置会促进淋巴管中的转移。
