Venous Nanoflap Oscillations: Biomechanical Determinants and Hydrodynamic Consequences in the Deep Cerebral Venous System

The most recent research has demonstrated that oscillatory nano-structures found on the lumenal walls of deep cerebral veins likely contribute significantly to the regulation of the function of deep cerebral veins. The oscillatory nano-structures consist of very small, intricately organized “nanoflaps,” each consisting of a hinge element with an attached lipid bilayer architecture. These nanoflaps have distinct mechanical properties, are in close proximity to mechanically sensitive protein assemblies, and therefore it is hypothesized that the nanoflaps generate rhythmic oscillations that control the distribution of both pressure and fluid flow through the veins and also regulate the metabolic condition of the surrounding tissue. In addition, the behavior of the nanoflaps indicate that there exists a hitherto unappreciated level of venous biomechanics at the nanometer scale that regulates the hydraulic stability of the veins and may also contribute to the structural integrity of the surrounding tissues. The purpose of this review is to provide a theoretical framework for understanding the recent discoveries of the structure, oscillation and hydrodynamic effects of nanoflaps, including resonance drift, waveform irregularity, and multi-scale biomechanical interactions. Additionally, this review will present the idea that disruption of the normal oscillatory processes that occur in the nanoflaps may lead to the development of abnormal micro-environments in the early stages of neurodegenerative diseases, abnormalities of compliance, dysautonomic states, traumatic injury and micro-circulatory stress. Finally, this review will describe several pharmacological strategies that may be used to stabilize the oscillations generated by the nanometer-scale oscillatory nano-structure by modifying the torque applied to the hinge, the viscoelasticity of the membrane and the feedback pathways for mechanotransduction.