Lead: Researchers at the University of Houston and Rutgers University report a theoretical mechanism by which tiny, active ripples in the lipid membranes that surround cells could produce usable electrical voltages. Published in PNAS Nexus in 2025, the model couples known membrane fluctuations driven by protein activity and ATP consumption with the material property called flexoelectricity. Their calculations suggest those ripples can generate transmembrane voltages up to about 90 millivolts on millisecond timescales — amplitudes and timing comparable to signals in excitable cells. If validated, the effect could help explain ion movement, coordinated tissue responses, and inspire bio‑inspired materials and computing designs.
Key Takeaways
- The theoretical model (Khandagale et al., PNAS Nexus, 2025) links active membrane fluctuations and flexoelectricity to produce transmembrane voltages up to ~90 mV, a magnitude comparable to neuronal thresholds.
- Predicted voltages emerge on millisecond timescales, matching the temporal window of nerve impulses and fast cellular signaling.
- Active drivers in the model include protein conformational activity and ATP hydrolysis, both established sources of non‑equilibrium membrane motion.
- The mechanism could assist directed ion transport across membranes, potentially influencing muscle contraction, sensory transduction, or coordinated tissue phenomena.
- Authors propose the effect can scale across coupled cells, enabling larger‑scale polarization in tissues rather than remaining a purely local phenomenon.
- Applications suggested include bio‑inspired neuromorphic materials and energy‑harvesting synthetic membranes, although experimental validation is pending.
Background
Cell membranes are thin lipid bilayers embedded with proteins that constantly move, bend and remodel. Thermal agitation produces random membrane undulations, but living cells are not at thermal equilibrium: proteins change shape and ATP is consumed in organized, stochastic ways that drive additional mechanical fluctuations. Historically, membrane fluctuations have been studied to understand mechanical properties, diffusion of membrane components and how proteins sense curvature, but attention to their electromechanical consequences has been limited.
Flexoelectricity is a material property in which spatial gradients of strain or curvature produce electrical polarization. It is a well‑known effect in synthetic and biological thin films: bending a membrane can separate charge. Under strict thermodynamic equilibrium, such microvolt‑level contributions average out and cannot power work. The new study pivots on the fact that cellular membranes are persistently driven by active, energy‑consuming processes, which can bias fluctuations away from simple equilibrium averaging.
Main Event
The authors constructed a theoretical framework that combines measured magnitudes of active membrane fluctuations with flexoelectric coupling constants reported for lipid bilayers. Using perturbative and numerical calculations, they estimate that realistic values of activity and flexoelectric coefficients yield transmembrane voltage differences up to approximately 90 millivolts in local regions. That magnitude is comparable to differences needed to depolarize neurons and initiate action potentials in some contexts.
Importantly, the model predicts these voltages arise on millisecond timescales, because the same active forces that push membranes also fluctuate at those rates. The timing aligns with fast ion channel kinetics and electrical signaling, which suggests membrane‑generated voltages could, in principle, modulate or bias ion channels rather than replace canonical ionic currents entirely. The authors emphasize a coupling: active bending produces polarization, and polarization can alter ion fluxes.
The study also explores how electro‑mechanical effects could coordinate across adjacent cells. If neighboring membranes fluctuate coherently or are mechanically coupled through junctions or extracellular matrix, local voltages could sum or bias tissue‑scale polarization. The result is a speculative pathway for emergent electrical patterns that do not rely solely on classical gap‑junction or synaptic transmission mechanisms.
Analysis & Implications
Biologically, a membrane‑level source of voltage could provide a supplementary bias to ion channels and pumps, lowering energetic costs for certain transport events or shaping excitability thresholds. For example, a localized 10–90 mV bias could assist ion entry or exit and influence how easily a neuron or muscle fiber reaches action potential threshold. However, the model does not claim membrane flexoelectricity is the primary driver of action potentials; rather it suggests a modulatory role that could be significant in particular cellular contexts.
The calculations depend on parameters that vary between cell types: membrane composition, embedded protein density, ATP consumption rates and flexoelectric coefficients. Those coefficients are sensitive to lipid makeup and experimental measurement techniques, so the absolute voltage estimates carry uncertainty. Demonstrating the effect in living tissue will require simultaneous high‑speed mechanical and electrical measurements with spatial resolution at the scale of nanometers to micrometers.
Beyond physiology, the proposed mechanism opens routes for engineered systems. Designers of synthetic membranes, sensors or neuromorphic hardware might harness active flexoelectricity to create low‑power, mechanically driven electrical signals. The authors specifically note implications for artificial neural networks and bio‑inspired computational materials that transduce mechanical fluctuations into directed electrical activity.
Comparison & Data
| Parameter | Typical value (biology) | Model prediction |
|---|---|---|
| Resting membrane potential (neuron) | ≈ −65 to −70 mV | — |
| Action potential threshold | ≈ −55 mV (varies) | Local bias up to ~90 mV |
| Predicted generation timescale | Ion channel kinetics: ms | ms‑scale membrane voltage pulses |
The table summarizes how the predicted flexoelectric voltages compare with canonical electrical values in excitable cells. While resting potentials are established by ionic gradients and active pumps, the modeled membrane‑generated voltages are comparable in magnitude and timing to physiological signals, which is why they may modulate excitability if realized in vivo.
Reactions & Quotes
Researchers present the findings cautiously, framing them as a theoretical demonstration that activity plus flexoelectricity can amplify transmembrane polarization. Independent experimental confirmation is a key next step.
“Cells are not passive systems — they are driven by internal active processes such as protein activity and ATP consumption,”
Khandagale et al., PNAS Nexus (2025)
This line emphasizes that the mechanism relies on persistent non‑equilibrium activity. The authors later underline the functional possibility rather than certainty.
“Activity can significantly amplify transmembrane voltage and polarization,”
Khandagale et al., PNAS Nexus (2025)
That phrasing signals the paper’s main claim: activity can boost electrically relevant signals. Outside experts quoted in media coverage note the result is provocative but requires controlled physiological tests before assigning a direct biological role.
Unconfirmed
- Direct experimental observation of flexoelectric‑driven voltages of ~90 mV in living cells is not yet reported; current support is theoretical and model‑based.
- Whether such voltages can reliably trigger action potentials in intact neural tissue under physiological conditions remains unproven.
- The extent to which membrane composition and cellular context modulate flexoelectric coefficients and active fluctuation amplitudes in vivo is uncertain.
Bottom Line
The PNAS Nexus study provides a carefully argued theoretical route by which active membrane fluctuations and flexoelectricity could produce biologically relevant voltages. The predicted amplitudes and timescales map onto known electrical signaling windows, making the mechanism plausible as a modulatory influence on ion transport and excitability rather than a wholesale replacement of established ionic mechanisms.
Confirming physiological relevance requires targeted experiments that measure membrane curvature, local polarization and ionic currents together in living cells and tissues. If verified, the idea would reshape aspects of membrane biophysics and inspire engineered systems that turn mechanical activity into directed electrical signals.