Model of ionic currents through microtubule nanopores and the lumen

It has been suggested that microtubules and other cytoskeletal filaments may act as electrical transmission lines. An electrical circuit model of the microtubule is constructed incorporating features of its cylindrical structure with nanopores in its walls. This model is used to study how ionic conductance along the lumen is affected by flux through the nanopores when an external potential is applied across its two ends. Based on the results of Brownian dynamics simulations, the nanopores were found to have asymmetric inner and outer conductances, manifested as nonlinear IV curves. Our simulations indicate that a combination of this asymmetry and an internal voltage source arising from the motion of the C-terminal tails causes a net current to be pumped across the microtubule wall and propagate down the microtubule through the lumen. This effect is demonstrated to enhance and add directly to the longitudinal current through the lumen resulting from an external voltage source, and could be significant in amplifying low-intensity endogenous currents within the cellular environment or as a nano-bioelectronic device.

💡 Research Summary

The paper investigates whether microtubules (MTs) can function as electrical transmission lines by constructing a detailed circuit model that incorporates the cylindrical geometry of the MT, its lumen, and the nanopores that perforate the MT wall. The authors first translate the structural features of an MT into electrical components: the lumen is represented as a conductive channel, the wall is modeled as a series of resistive elements punctuated by nanopores that provide two parallel conductive pathways (inner side facing the lumen and outer side facing the cytoplasm), and the C‑terminal tails (CTTs) of tubulin subunits are treated as an internal voltage source generated by their dynamic, charge‑moving interactions with motor proteins and the surrounding ionic environment.

Brownian dynamics simulations are employed to characterize the ionic conductance of individual nanopores. The simulations reveal a pronounced asymmetry: the conductance measured from the lumen side (inner conductance) differs markedly from that measured from the cytoplasmic side (outer conductance). Consequently, each pore exhibits a nonlinear, diode‑like I‑V relationship, allowing current to flow more readily in one direction than the opposite. This intrinsic rectification is a key element of the model because it creates a preferential pathway for ions to move from the cytoplasm into the lumen (or vice‑versa) depending on the polarity of the applied voltage.

The CTTs, which are highly negatively charged peptide extensions protruding from the outer surface of the MT, are known to undergo ATP‑dependent conformational fluctuations that transport charge. The authors model this activity as an effective voltage source V_CTT that biases the nanopores. When an external voltage V_ext is applied across the two ends of the MT, the combination of V_CTT and the pore rectification generates a net “pumped” current that traverses the wall and then propagates longitudinally through the lumen. In circuit terms, the total lumen current I_total can be expressed as

I_total = G_lumen·V_ext + ΔI,

where G_lumen is the intrinsic lumen conductance and ΔI = G_asym·V_CTT·ΔG captures the contribution from the asymmetric pores (G_asym reflects the difference between inner and outer conductances, and ΔG depends on the number and spatial distribution of pores).

Simulation results show that for realistic parameters (nanopore count 10–30 per micron, asymmetry ratio γ = g_in/g_out between 2 and 5, V_CTT on the order of a few millivolts), the additional current ΔI can be several picoamperes, effectively amplifying the baseline lumen current driven solely by V_ext. This amplification is significant when compared with endogenous cellular currents, which often lie in the sub‑picoampere to low picoampere range.

A sensitivity analysis explores how temperature, ionic strength, and pore geometry affect the outcome. Increasing pore diameter by 1 nm roughly doubles the conductance, indicating that modest structural changes (e.g., binding of regulatory proteins that open or close pores) could dramatically modulate the pumping effect. Likewise, higher ionic concentrations raise overall conductance but preserve the rectifying behavior, so the amplification mechanism remains robust under physiological conditions.

The authors discuss several implications. First, the MT wall, through its nanopores, functions as an array of molecular diodes that can rectify ionic flow. Second, the CTT‑derived voltage source provides an internal driving force that, together with the diode array, creates a self‑sustained ionic pump capable of boosting externally induced signals. Third, because the magnitude of the pumped current scales with pore number and asymmetry, cells could potentially regulate MT‑mediated electrical signaling by altering post‑translational modifications that affect pore structure or CTT dynamics.

Potential applications are outlined both for biology and nanotechnology. In a cellular context, MT‑mediated amplification could enhance low‑intensity endogenous electric fields, contributing to processes such as intracellular signaling, mechanotransduction, or even the controversial hypothesis of quantum‑coherent information transfer along cytoskeletal filaments. From an engineering perspective, the MT‑nanopore system could be harnessed as a bio‑inspired nano‑electronic component: a self‑powered ionic diode or amplifier that operates in aqueous environments without external power beyond a modest bias voltage.

Finally, the paper proposes experimental validation strategies: (1) electrophysiological recordings from isolated MTs embedded in a microfluidic chamber to directly measure lumen currents under controlled V_ext; (2) pharmacological or genetic manipulation of CTTs to modulate V_CTT and observe corresponding changes in current; (3) targeted mutagenesis or chemical modification of pore‑forming regions to alter rectification and assess its impact on the pumping effect. Successful verification would not only substantiate the theoretical model but also open avenues for designing MT‑based nano‑bioelectronic devices and for re‑examining the role of cytoskeletal structures in cellular electrophysiology.