Dynamic and Fatigue Analysis of Healthy and Diseased Red Blood Cells

红细胞在体内循环时经历了大量的剪切、拉伸和弯曲。在循环细胞被移除并被新细胞取代之前，会发生进行性损伤。细胞生物力学的大部分研究都集中在单一的负荷应用上，而不是复制细胞在体内所经历的动态重复负荷。这项研究将使用一种新的微流体工具来应用重复的细胞加载，从而对循环红细胞损伤的机械起源有一个基本的了解。该结果将提供细胞生物力学和细胞生物学之间的定量联系，从而促进我们对输血红细胞寿命显著缩短和疾病导致红细胞异常的理解。多学科方法将扩大未被充分代表的群体在科学和工程领域的参与。PI特别强调鼓励女学生参与工程和生命科学交叉领域的研究。本研究的目的是建立人体红细胞的细胞动力学和疲劳特性、体内循环历史和病理生理因素的影响之间的基本关系。这项工作具体解决了以下问题：(a)如何以相对高的通量实现单个细胞的动态粘弹性和疲劳测量，以及(b)如何量化对细胞生物力学的病理生理影响。本研究将整合微流体学、交流电动力学、数字调制和生物力学的知识和技术，开发单细胞动态和疲劳测量的实验策略。循环中的机械力对细胞膜的损伤过程与材料疲劳有明显的相似之处。实验确定的Wöhler曲线结合Miner法则将用于预测受体内衰老和镰状细胞病影响的红细胞剩余寿命。本研究的新颖之处在于新的实验策略和细胞生物力学的新视角。

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.