CAREER: Multi-Scale Approaches to Quantify Biomechanical Control of Lymphatic Pump Function

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

The research objective of this Faculty Early Career Development (CAREER) Program award is to investigate ways in which the coordination of the lymphatic pump is self-regulated such that transient changes in vessel mechanical loading provide a cue to orchestrate the contractile sequences in adjacent vessel segments. Lymphatic muscle cells contract the vessel to move fluid form the interstitium against a pressure gradient. It is unclear how biomechanics regulate the timing and function of lymphatic contraction across short time scales. The objective will be addressed by performing a system identification of the primary lymphatic contractile unit in order to characterize the pump function response to the variety of biomechanical conditions experienced in the body. The experiments will seek to demonstrate that these phenomena are driven by calcium signaling and regulated in part via release of endothelin-1 and nitric oxide within the vessel. These hypotheses will be tested across multiple length scales using in-vitro biomechanical tissue culture devices, feedback-controlled isolated vessel perfusion systems, and in-vivo near infrared (NIR) imaging. Understanding how lymphatic biology utilizes biomechanics to regulate and coordinate its drainage response to varying demands will not only provide key insight into diseases such as lymphedema, but it will also provide bio-inspired design approaches for developing artificial drainage networks in tissue engineering and nanotechnology that function in an as-needed fashion. The educational plan for this award seeks to address the current disparity in lymphatic training and research. Teaching modules on lymphatic physiology will be implemented at a nearby medical school and research results will be integrated into a graduate level Biotransport course to provide students with unsolved engineering problems in lymphatic biomechanics through problem-based learning. Lastly, elementary students will be engaged in interactive research-based science education, where they will be exposed to the impact of bioengineering approaches in medicine.