New method reveals how damage occurs in human biological cells due to mechanical fatigue

Fatigue testing of cells
Fatigue testing of single RBCs using amplitude-modulated electrodeformation. (A) Experimental setup for real-time measurement of cell deformation in a microfluidic chip. Schematic shows the key components of the testing system, including the microfluidic device with interdigitated microelectrodes, signal generator for producing modulated sinusoidal carrier wave, and computer for data acquisition, analysis, and modeling. (B) Microscopic images of a representative RBC when the electric field (E-field) is ON and OFF. Dimensions of RBC are measured along x and y axes (a and b, respectively). (C) Microscopic images of cell deformation at 4 representative loading levels arising from applied voltages of 0.5, 0.8, 1.0, and 1.2 V as functions of loading cycles (N = 1, 50, 450, and 900). (Scale bars in B and C, 5 μm.) Credit @ Yuhao Qiang, Jia Liu, Ming Dao, Subra Suresh, and E. Du

Human red cells (RBCs) are very versatile and have the ability to experience cell deformation as they move around different small vessels and capillaries. Their average life time is around 120 days and during this time, RBCs experience cyclic stretching and relaxation and it can be relatively large. However under several diseases such as myocardial infarction, diabetes and other disorders, the RBCs deform abnormally.

In mechanical engineering it is known that cyclic loading leads to fatigue – phenomenon leaded to many machine failures. Fatigue can also damage and create cracks in biomaterials, such as bones, but also in synthetic biomaterials, which are used in dental implants or artificial heart valves.  Apparently, this cyclic straining also leads to fatigue in the RBCs.  However, the degradation mechanisms involved in fatigue in biological cells is not understood. Measuring fatigue response of healthy and diseased biological cells has been a challenge for decades.

Recently, researchers from Florida Atlantic University’s College of Engineering and Computer Science, Massachusetts Institute of Technology and the Nanyang Technological University in Singapore, have built up a novel method to quantify the impact of the mechanical fatigue on the behavior of natural cells. They have found the significant effect of the fatigue on physical properties of natural cells, such as RBCs.

The results of the research also give hints into the accumulation of the damage of the cells membranes during blood re-circulation. Future investigation may address the eventual failure of the RBCs and the mechanisms of cells degradation under different blood diseases.

The newly developed procedure evaluates the mechanical strength and fatigue behavior of RBCs utilizing a general microfluidics technique that employs amplitude-modulated electro-deformation. It applies static and cyclic mechanical deformation to RBCs and measures precisely the changes in morphological and biomechanical qualities of healthy human RBCs and the mechanical properties of their membranes. This strategy allows also to apply static loads for longs periods, as well as a large amount of fatigue cycles.  The approach allows to quantify mechanical fatigue behavior of individual cells, but also it is relatively simple and flexible. The flexibility allows to apply the load in static or cyclic manner, but also to study one or several cells at a time.

The scientists needed to address the impact of changes in stresses or deformations of a biological cell on its mechanical and physical attributes, and performance. The results from the examination further show that loss of deformability of RBCs during cyclic deformation is a lot quicker than that under static deformation at same maximum load and over the same time. The defomability loss is also more pronounced at higher amplitudes of the deformation cycles.

Further information: Yuhao Qiang et al, Mechanical fatigue of human red blood cells, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1910336116

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