Anish Mukherjee

Lymphedema, a debilitating disease characterized by excess interstitial fluid accumulation in the extremities of the body, is suspected to be caused by dysfunctions in the lymphatic system. Elevated transmural pressure and wall shear stress in studies on isolated lymphatic vessels have been shown to modify the lymphatic vessel function, although the focus has been put on functional changes in response to constant mechanical loading. However, the underpinning molecular details and the frequency limitations of the lymphatic vessel response to dynamic pressure and shear stress waveforms are unknown. Hence the present work will try to quantify the effects of oscillatory mechanical forces on the function of lymphatic vessels by 1) Ex vivo quantification of the contractility of isolated lymphatic vessels modified in response to oscillatory shear stresses, 2) In vitro quantification of the calcium dynamics in lymphatic endothelial cells in response to oscillatory shear stress and stretch and 3) In vivo quantification of the change in lymphatic pumping metrics, obtained by NIR imaging, in response to steady and oscillatory external pressure waveforms in a rat model. This work will inform studies on molecular mechanisms leading to mechanosensitivity of lymphangions and will provide experimental evidence for improved physiotherapy techniques for lymphedema.