Mass Transfer Phenomena in the Lymphatic System

The primary aim of this research project is to quantify the contractility of lymphatic muscle cells (LMCs) across multiple scales for a range of diastolic diameters and transmural pressures. This aim is motivated by the importance of contractile force in lymph propulsion and the generation of pressure differences required for the function of lymphatic valves. The knowledge gained from this research will be incorporated into multi-scale models of flow in the lymphatic system, which are based on lumped parameter and computational mass transport approaches. This is to be done using both experimental and computational methods, with the main experiments being performed by collaborators and theoretical models then being developed as part of the research project. The experiments will be performed to obtain data required for determining contractile force as a function of the upstream and downstream pressures. Two series of experiments will be performed, the first series will consist of cannulating lymphatic vessels, varying the pressure and measuring both the internal and external vessel diameters. The second series of experiments will use a wire myograph to determine the length-tension relationship of isolated lymphatic vessels. This project will then use computational methods required to process the experimental results because the contractility of the LMCs can only be measured indirectly. The determination of contractility from experimental results is to be based on balancing the circumferential forces. Geometrical data and measurements of the pressure within the lymphangion from the first series of experiments will be combined for the calculation of contractile force. Analysis of the second series of experiments will calculate the contractile tension from measurements of the force transducer and average wall thickness, and the results will be compared with a finite element model of five or more lymphangions. Further modelling based on current models of smooth muscle cells will be required for incorporation of the contractility into the lymphatic flow models. This research will be original as there is currently no single model of smooth muscle that can be applied to all systems and the smooth muscle in lymphatics is significantly different from that in the systems which have been the focus of research. This research will therefore be the first to quantify and model the contractility of LMCs over the physiologic range.

The project will also include involvement in the other research aims of the research group, which are to characterize the resistance and hysteresis of lymphatic valves, and to develop models of fluid flow and leukocyte behaviour in lymph nodes. The results from these aims will also be incorporated into multi-scale models of the transport phenomena of the lymphatic system. Characterization of the lymphatic valves will involve experimental characterization of valves and computational models of the solid and fluid mechanics involved, which will ultimately be combined in a fluid-structure interaction model. Modelling the lymph nodes will involve computational fluid dynamics of lymph flow through the node, and agent-based modelling of the cells in lymph nodes. The computational fluid dynamics and agent-based models will ultimately be coupled to provide a more comprehensive model of lymph nodes.