Cellular and Extracellular Homeostasis in Fluctuating Mechanical Environments

  • Béla SukiEmail author
  • Harikrishnan Parameswaran
  • Calebe Alves
  • Ascânio D. Araújo
  • Erzsébet Bartolák-Suki
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 23)


Homeostasis is considered to be a cellular feedback mechanism that maintains a target such as mean blood pressure at a well-defined level, which is called upward causation. In this chapter, we consider a downward causation in which higher level properties are not only sensed by cells, but they also cause changes in cellular level behavior. Specifically, we examine how fluctuations at the level of the target, such as beat-to-beat blood pressure variability, present themselves as boundary conditions at the level of the cell and how this affects cellular behavior such cytoskeletal structure or homeostasis of bioenergetics. The changes in low level mechanisms may feed back to the regulation of the target until some homeostasis is achieved in which the system is under far from equilibrium conditions but without ever reaching a steady state. Consequently, the target is allowed to fluctuate within homeostatic limits. We will first summarize current concepts in conventional mechanotransduction and then discuss the dynamic aspects of mechanotransduction in the presence of noisy mechanical inputs, called fluctuation-driven mechanotransduction (FDM). Next, we will demonstrate how FDM alters cytoskeletal organization using a computational model of the actin-myosin network under time-varying strain boundary conditions in which peak strains vary from cycle to cycle. The simulation results imply that FDM should be considered as an emergent multiscale network phenomenon. In vascular smooth muscle cells, cytoskeletal structural alterations also lead to mitochondrial remodeling with subsequent changes in ATP production. The latter affects cell contractility as well as bioenergetics which in turn feed back to collagen maintenance, vascular wall stiffness and ultimately blood pressure regulation. We argue that FDM is a general phenomenon that other cell types also exhibit such as enhanced surfactant production by lung epithelial cells due to tidal volume variability. Following some speculation on the possible roles of fluctuations in diseases and aging, we will offer a general picture of how the breakdown of FDM disturbs homeostasis which can lead to the pathogenesis of diseases.


Mechanotransduction Network Cytoskeleton Mitochondria Disease Aging 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Béla Suki
    • 1
    Email author
  • Harikrishnan Parameswaran
    • 2
  • Calebe Alves
    • 3
  • Ascânio D. Araújo
    • 3
  • Erzsébet Bartolák-Suki
    • 1
  1. 1.Department of Biomedical EngineeringBoston UniversityBostonUSA
  2. 2.Department of Biomedical EngineeringNortheastern UniversityBostonUSA
  3. 3.Departamento de FísicaUniversidade Federal do CearáFortalezaBrazil

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