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Dynamic modeling and control of extracellular ATP concentration on vascular endothelial cells via shear stress modulation

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Abstract

A new dynamic model for cell-deformation-induced adenosine triphosphate (ATP) release from vascular endothelial cells (VECs) is proposed in this paper to quantify the relationship between the ATP concentration at the surface of VECs and blood flow-induced shear stress. The simulation results demonstrate that ATP concentration at the surface of VECs predicted by the proposed new dynamic model is more consistent with the experimental observations than those by the existing static and dynamic models. Furthermore, it is the first time that a proportional-integral-derivative (PID) feedback controller is applied to modulate extracellular ATP concentration. Three types of desired ATP concentration profiles including constant, square wave and sinusoid are obtained by regulating the wall shear stress under this PID control. The systematic methodology utilized in this paper to model and control ATP release from VECs via adjusting external stimulus opens up a new scenario where quantitative investigations into the underlying mechanisms for many biochemical phenomena can be carried out for the sake of controlling specific cellular events.

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Authors and Affiliations

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Correspondence to Cheng Xiang.

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The work was supported by NUS Academic Research Fund (R-263-000-483-112).

Cheng XIANG received the B.S. degree from Applied Mechanics, Fudan University, China, in 1991, the M.S. degree in Mechanical Engineering from the Institute of Mechanics, Chinese Academy of Sciences, in 1994, and the M.S. and Ph.D. degrees in Electrical Engineering from Yale University, New Haven, CT, in 1995 and 2000, respectively. From 2000 to 2001, he was a financial engineer at Fannie Mae, Washington, D.C. Currently, he is an associate professor in the Department of Electrical and Computer Engineering, National University of Singapore. His research interests include computational intelligence, adaptive systems, and pattern recognition.

Lingling CAO received the B.S. degree from Applied Mechanics, Fudan University, China, in 2006. She is currently a Ph.D. student in the Department of Electrical and Computer Engineering, National University of Singapore.

Kairong QIN received the B.S. degree from Applied Mechanics, Fudan University, China, in 1991. He continued his study in Fluid Mechanics (Biomechanics), Fudan University, China, and received the Ph.D. degree in 1996. He is currently a research fellow in the Department of Electrical and Computer Engineering, National University of Singapore. His research interests include biomechanics and modeling in mechanobiology, modeling and control in microfluidics-based systems biology, and signal processing in biomedicine.

Tong Heng LEE received the B.A. degree with First Class Honors in the Engineering Tripos from Cambridge University, England, in 1980 and the Ph.D. degree from Yale University in 1987. He is a professor in the Department of Electrical and Computer Engineering at the National University of Singapore (NUS) and also a professor in the NUS Graduate School, NUS NGS. He was a past vice-president (research) of NUS. Dr. Lee’s research interests are in the areas of adaptive systems, knowledge-based control, intelligent mechatronics and computational intelligence. He currently holds associate editor appointments in the IEEE Transactions in Systems, Man and Cybernetics; IEEE Transactions in Industrial Electronics; Control Engineering Practice (an IFAC journal); and the International Journal of Systems Science (Taylor and Francis, London). In addition, he is the deputy editor-in-chief of IFAC Mechatronics journal. Dr. Lee was a recipient of the Cambridge University Charles Baker Prize in Engineering; the 2004 ASCC (Melbourne) Best Industrial Control Application Paper Prize; the 2009 IEEE ICMA Best Paper in Automation Prize; and the 2009 ASCC Best Application Paper Prize. He has also co-authored five research monographs (books) and holds four patents (two of which are in the technology area of adaptive systems, and the other two are in the area of intelligent mechatronics). He has published more than 300 international journal papers. Dr. Lee was an invited panelist at the World Automation Congress, WAC2000, Maui, U.S.A.; an invited keynote speaker for the IEEE International Symposium on Intelligent Control, IEEE ISIC 2003 Houston, U.S.A.; an invited keynote speaker for LSMS 2007, Shanghai, China; an invited expert panelist for IEEE AIM2009; and an invited plenary speaker for IASTED RTA 2009.

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Xiang, C., Cao, L., Qin, K. et al. Dynamic modeling and control of extracellular ATP concentration on vascular endothelial cells via shear stress modulation. J. Control Theory Appl. 8, 326–332 (2010). https://doi.org/10.1007/s11768-010-0030-y

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