Charged Interfaces in the Brain: How Electrostatic Forces May Guide Cerebrospinal Fluid Dynamics

Cerebrospinal fluid (CSF) flows play a main role in maintaining brain homeostasis, supporting waste clearance, nutrient delivery and interstitial solute exchange. Although current models emphasize mechanical drivers such as cardiac pulsation, respiration and ciliary motion, these mechanisms alone fall short of explaining the nuanced spatiotemporal regulation of CSF flow observed under physiological and pathological conditions—even when accounting for the glymphatic framework. We explore the hypothesis that electrostatic forces arising from charged cellular interfaces may contribute to CSF movement through electro-osmotic mechanisms. We begin by examining the biological basis for surface charge in the brain, highlighting the presence of charged glycoproteins, ion channels and dynamic membrane potentials on ependymal and glial cells interfacing directly with CSF pathways. Next, we describe key principles of electro-osmosis in confined geometries, emphasizing how nanoscale surface charges can modulate fluid motion without mechanical input. Drawing from nanofluidic research and electrohydrodynamic theory, we argue that the conditions required for electro-osmotic coupling, i.e., ionic fluid, narrow conduits and patterned surface charge, are present within brain microenvironments. To test plausibility, we present computational simulations demonstrating that surface charge patterns alone can induce structured fluid flow and solute transport, including nonlinear transitions and oscillatory behaviours that resemble physiological rhythms. These findings support the idea that electrostatics may play a modulatory role in CSF regulation, complementing mechanical drivers. Overall, by integrating concepts from neuroscience, biophysics and nanotechnology, we propose a testable, mechanistically grounded hypothesis reframing CSF dynamics as electrohydrodynamically sensitive processes, with potential implications for understanding brain function and dysfunction.