Mass Transfer Phenomena in the Lymphatic System

Lead Research Organisation: Imperial College London
Department Name: Dept of Bioengineering

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 01/10/2016 31/03/2022
1846150 Studentship EP/N509486/1 01/10/2016 31/03/2020 Christopher Morris
 
Description The lymphatic system is responsible for fluid homeostasis. Lymphatics do not, however, have a central pump equivalent to the heart. This means that the lymphatic vessels themselves must pump. Vessel pumping is achieved by a combination of external compression and intrinsic muscle contractions. Intrinsic contractions must fulfil the roles of the heart (generate flow) and blood vessels (regulate flow) A computational model has been developed that describes how both rapid (flow generation) and longer term (flow regulation) contractions of lymphatic muscle interact and the effect this has on lymph flow. The necessary introduction of passive elements in a cell-scale model of lymphatic muscle in order to capture physiologic responses has offered some insight into the subcellular structure. The responses of lymphatic muscle contractions to varying pressure have been studied which allowed more detailed knowledge of how the two contraction types interacted, and gave information on the energetic efficiency o lymphatic muscle. Sensitivity of the model to calcium binding properties has been examined to inform potential future developments of the model incorporating regulation of muscle contractions.
Exploitation Route There are several possible improvements that could be made to the model. One such improvement would be a more detailed representation of contraction triggering. Studying the response of the model to different inputs will help to understand how lymphatic muscle functions and how it fails. The model results will also be used to suggest future experiments using a device being developed in the same research group that allows culturing of lymphatic muscle without losing its contractile phenotype (as occurred previously). Such experiments will likely involve studying the energy efficiency of lymphatic muscle contractions.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology