[Paper Review] Experimental evidence for long-distance electrodynamic intermolecular forces

Mathias Lechelon, Yoann Meriguet+13 more|arXiv (Cornell University)|Feb 17, 2022

Biofield Effects and Biophysics59 references45 citations

TL;DR

This study presents the first experimental evidence of long-range dipole-dipole electrodynamic (ED) forces between biomolecules, demonstrating resonant ED interactions in R-Phycoerythrin proteins via terahertz spectroscopy and fluorescence correlation spectroscopy. The forces, active up to 1000 Å and activated by laser-induced collective molecular oscillations, show a frequency shift inversely proportional to the cube of intermolecular distance, indicating selective, long-range attraction that could enhance molecular encounter rates in crowded cellular environments.

ABSTRACT

Both classical and quantum electrodynamics predict the existence of dipole-dipole long-range electrodynamic intermolecular forces; however, these have never been hitherto experimentally observed. The discovery of completely new and unanticipated forces acting between biomolecules could have considerable impact on our understanding of the dynamics and functioning of the molecular machines at work in living organisms. Here, using two independent experiments, on the basis of different physical effects detected by fluorescence correlation spectroscopy and terahertz spectroscopy, respectively, we demonstrate experimentally the activation of resonant electrodynamic intermolecular forces. This is an unprecedented experimental proof of principle of a physical phenomenon that, having been observed for biomacromolecules and with long-range action (up to 1000 Angstroms), could be of importance for biology. In addition to thermal fluctuations that drive molecular motion randomly, these resonant (and thus selective) electrodynamic forces may contribute to molecular encounters in the crowded cellular space.

Motivation & Objective

• . To experimentally detect long-range electrodynamic (ED) intermolecular forces predicted by classical and quantum electrodynamics but never observed before.
• . To investigate whether out-of-equilibrium collective oscillations in proteins can activate resonant ED forces with long-range action.
• . To test the hypothesis that such ED forces could enhance molecular association rates in the crowded cellular environment beyond random diffusion.
• . To overcome the technical challenge of detecting THz signals in aqueous, ionic solutions by developing two novel near-field THz sensing setups.
• . To validate the existence of ED forces through dual, independent experimental techniques: THz spectroscopy and fluorescence correlation spectroscopy (FCS).

Proposed method

• . Used R-Phycoerythrin (R-PE) as a model protein system, excited by a 488 nm blue laser to induce out-of-equilibrium collective dipole oscillations.
• . Employed two distinct THz spectroscopy setups: a rectenna-based sensor (0.07–0.11 THz) and a microwire-probe sensor (0.25–0.37 THz), both designed to detect weak THz signals in aqueous, saline solutions.
• . Applied Beer–Lambert normalization to isolate the absorbance of laser-excited proteins by subtracting buffer and non-illuminated controls.
• . Conducted fluorescence correlation spectroscopy (FCS) to measure changes in diffusion coefficients as a function of protein concentration and laser power.
• . Analyzed data using Savitsky–Golay smoothing (15-point window, 2nd order polynomial) and time-dependent peak amplitude tracking for resonance frequencies.
• . Used the Smoluchowski-Debye formula to model association rate enhancement due to attractive ED potential U(r) < 0.

Experimental results

Research questions

• RQ1 . Can long-range electrodynamic dipole-dipole forces be experimentally observed in biological macromolecules under physiological conditions?
• RQ2 . Does laser-induced collective molecular oscillation in proteins activate resonant ED interactions with measurable frequency shifts?
• RQ3 . Is the frequency shift of collective oscillations inversely proportional to the cube of the intermolecular distance, as predicted by ED theory?
• RQ4 . Can THz spectroscopy detect these forces in aqueous, ionic solutions despite strong water absorption?
• RQ5 . Do changes in protein diffusion coefficients measured by FCS correlate with the onset of ED interactions at specific concentrations and excitation powers?

Key findings

• . A frequency shift in collective molecular oscillations was observed in R-PE proteins, with a shift inversely proportional to the cube of the intermolecular distance, consistent with long-range dipole-dipole electrodynamic interactions.
• . The shift in resonance frequency was experimentally confirmed across multiple protein concentrations (from 750 nM to 60,000 nM) and laser powers, with a clear dependence on excitation intensity.
• . A distributed-clustering transition was observed in FCS data, indicating the onset of long-range attractive forces at higher concentrations and laser powers, with diffusion coefficients decreasing significantly.
• . The normalized absorbance of excited proteins showed a time-dependent increase in peak amplitude over 60 minutes, indicating sustained ED interaction activation.
• . The rectenna-based setup detected a single absorption peak in the 0.07–0.11 THz range, while the microwire-probe setup revealed a time-evolving resonance in the 0.25–0.37 THz band, both consistent with ED force activation.
• . The observed association rate enhancement via ED forces, as modeled by the Smoluchowski-Debye formula, exceeds purely diffusive rates (k∗a > ka), indicating a measurable kinetic advantage in molecular encounters.