Li Huabing, Wei Huajian, Padera Timothy P, Baish James W, Munn Lance L
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Department of Material Science and Technology, Guilin University of Electronic Technology, Guilin 541004, China.
PNAS Nexus. 2022 Oct 18;1(5):pgac237. doi: 10.1093/pnasnexus/pgac237. eCollection 2022 Nov.
Physical forces, including mechanical stretch, fluid pressure, and shear forces alter lymphatic vessel contractions and lymph flow. Gravitational forces can affect these forces, resulting in altered lymphatic transport, but the mechanisms involved have not been studied in detail. Here, we combine a lattice Boltzmann-based fluid dynamics computational model with known lymphatic mechanobiological mechanisms to investigate the movement of fluid through a lymphatic vessel under the effects of gravity that may either oppose or assist flow. Regularly spaced, mechanical bi-leaflet valves in the vessel enforce net positive flow as the vessel walls contract autonomously in response to calcium and nitric oxide (NO) levels regulated by vessel stretch and shear stress levels. We find that large gravitational forces opposing flow can stall the contractions, leading to no net flow, but transient mechanical perturbations can re-establish pumping. In the case of gravity strongly assisting flow, the contractions also cease due to high shear stress and NO production, which dilates the vessel to allow gravity-driven flow. In the intermediate range of oppositional gravity forces, the vessel actively contracts to offset nominal gravity levels or to modestly assist the favorable hydrostatic pressure gradients.
物理力,包括机械拉伸、流体压力和剪切力,会改变淋巴管的收缩和淋巴流动。重力会影响这些力,导致淋巴运输发生改变,但其中涉及的机制尚未得到详细研究。在此,我们将基于格子玻尔兹曼的流体动力学计算模型与已知的淋巴力学生物学机制相结合,以研究在重力作用下,流体在淋巴管中的流动情况,重力可能会阻碍或促进流动。血管中规则间隔的机械双叶瓣膜在血管壁根据血管拉伸和剪切应力水平调节的钙和一氧化氮(NO)水平自主收缩时,强制实现净正向流动。我们发现,与流动方向相反的大重力会使收缩停止,导致无净流动,但短暂的机械扰动可重新建立泵血功能。在重力强烈促进流动的情况下,由于高剪切应力和NO的产生,收缩也会停止,这会使血管扩张以允许重力驱动的流动。在重力反向作用的中间范围内,血管会主动收缩以抵消名义重力水平或适度辅助有利的静水压力梯度。