Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells) caused by interstitial fluid flow. The numerical simulation results show the following: (i) the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii) when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii) interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv) capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

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Mechanical microenvironment plays a key role in the regulation of the phenotype and function of cardiac cells, which are strongly associated with the intracellular redox mechanism of cardiomyocytes. However, the relationship between the redox state of cardiomyocytes and their mechanical microenvironment remains elusive. In this work, we used polyacrylamide (PA) gels with varying stiffness (6.5−92.5 kPa) as the substrate to construct a mechanical microenvironment for cardiomyocytes. Then we employed scanning electrochemical microscopy (SECM) to in situ characterize the redox state of a single cardiomyocyte in terms of the apparent rate constant (k f ) of the regeneration rate of ferrocenecarboxylic by glutathione (GSH) released from cardiomyocyte, which is the most abundant reactant of intracellular reductive-oxidative metabolic cycles in cells and can represent the redox level of cardiomyocytes. The obtained SECM results show that the cardiomyocytes cultured on the stiffer substrates present lower k f values than those on the softer ones, that is, the more oxidative state of cardiomyocytes on the stiffer substrates compared to those on the softer ones. It proves the relationship between mechanical factors and the redox state of cardiomyocytes. This work can contribute to understanding the intracellular chemical process of cardiomyocytes during physiopathologic conditions. Besides, it also provides a new SECM method to in situ investigate the redox mechanism of cardiomyocytes at a single-cell level.

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