Dynamic and Fatigue Analysis of Healthy and Diseased Red Blood Cells

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Red blood cells experience a tremendous amount of shearing, stretching and bending as they circulate through the body. Progressive damage occurs in the circulating cells before they are removed and replaced with new ones. Much of the research on cellular biomechanics focuses on a single application of load, which does not reproduce the dynamic repetitive loading that the cells experience in the body. This research will use a new microfluidic tool to apply repetitive cell loading to create a fundamental understanding of the mechanical origins of damage in circulating red blood cells. The results will provide quantitative links between cellular biomechanics and cell biology, thus advancing our understanding of the significantly shortened lifespan of transfused red blood cells and those made abnormal by diseases. The multidisciplinary approach will broaden participation of underrepresented groups in Science and Engineering. The PI is placing special emphasis on encouraging women students to participate research at the interface of engineering and life sciences.The objective of this research is to establish the fundamental correlations between the cellular dynamic and fatigue properties, the in vivo circulation history and influences from pathophysiological factors in human red blood cells. This work specifically addresses questions: (a) how to implement the dynamic viscoelasticity and fatigue measurements of individual cells at a relatively high throughput, and (b) how to quantify the pathophysiological influences on cellular biomechanics. This research will develop an experimental strategy for dynamic and fatigue measurement of single cells, by integrating knowledge and techniques of microfluidics, alternating current electrokinetics, digital modulation and biomechanics. The damage process in cell membranes caused by the mechanical forces in circulation is significantly analogous to material fatigue. Experimentally determined Wöhler curves in combination with Miner's rule will be used for remaining life prediction in red blood cells influenced by in vivo aging and sickle cell disease. Novelty of this research lies in the new experimental strategy and a new perspective in cellular biomechanics.