Discovery claimed by LINkS

An international team coordinated by researchers at Aix-Marseille University and Montpellier University reports experimental evidence for long-distance electrodynamic intermolecular forces acting between proteins. The work, produced by the LINkS consortium and published in Science Advances on 16 February 2022, describes two independent experimental signatures that the authors interpret as activation of resonant dipole-dipole electrodynamic interactions among biomolecules when those molecules are driven out of thermal equilibrium.

The experiments were performed on a natural light-harvesting protein called R-phycoerythrin and on bovine serum albumin labeled with fluorochromes. The team used fluorescence correlation spectroscopy to detect abrupt changes in diffusion consistent with clustering and terahertz spectroscopy to measure concentration dependent frequency shifts of collective vibrational modes. The authors link both observations to a theoretical mechanism that predicts selective, resonant attraction with a potential falling like the cubic inverse of distance.

What the LINkS experiments report

LINkS reports two complementary experimental outcomes that together compose the claimed proof of principle. First, under optical pumping at blue wavelengths, R-phycoerythrin (R-PE) molecules in saline solution displayed a sudden transition from Brownian diffusion to slow clustered motion at a critical concentration. This was observed as a steep drop in the measured diffusion coefficient and as very large fluorescence fluctuations in fluorescence correlation spectroscopy experiments. Second, terahertz spectroscopy measurements showed that the frequency of collective vibrational modes of both R-PE and labeled bovine serum albumin (BSA) shifted with concentration in a manner the authors say matches the theoretically expected 1/〈r〉3 dependence, where 〈r〉 is the average intermolecular distance.

Key experimental parameters were maintained intentionally. Solutions contained 200 mM NaCl to screen electrostatic Coulomb interactions. Optical pumping used 488 nm light, with laser powers adjusted according to the measurement technique. The clustering transition for R-PE appeared in fluorescence correlation experiments at specific average intermolecular distances that shifted depending on the laser power. For R-PE the transition could occur within seconds under the high energy density of the confocal excitation volume, while terahertz spectral features required minutes of pumping in larger volumes.

Methods in more detail

LINkS combined experimental techniques with theoretical modelling and numerical simulation. The two laboratory methods were fluorescence correlation spectroscopy together with fluorescence cross correlation to monitor diffusion and clustering dynamics, and terahertz near-field spectroscopy to detect collective vibrational resonances and their concentration dependence. The team also used molecular dynamics, Langevin dynamics in the overdamped limit, Monte Carlo and semi-analytical models to predict the clustering phase transition and to compare with experimental thresholds.

The theoretical basis claimed by the authors

The LINkS team frames their findings within a body of theory that goes back to Fröhlich and to more recent classical formulations of electrodynamic dipole interactions among macromolecules. The mechanism requires molecules to sustain coherent low frequency collective vibrations while being driven out of thermal equilibrium. If two or more molecules oscillate at resonant frequencies, oscillating dipoles can couple through the electromagnetic field even in an electrolyte, provided the oscillation frequency is above the medium's Maxwell frequency so that Debye screening of static and low frequency fields is ineffective. Under these conditions a resonant interaction can behave effectively like a long-range potential falling as 1/r3 and displaying selectivity through frequency resonance.

Funding, consortium and publication

The LINkS project was supported by multiple sources. Core acknowledgment goes to funding linked to the European Innovation Council and to French and EU research programmes. The work was carried out by a consortium of research partners including teams at Aix-Marseille University (Centre de Physique Théorique and Centre d'Immunologie de Marseille-Luminy), Institut d'Electronique et des Systèmes at Montpellier University, and other contributors listed in the Science Advances article. The publication appeared in Science Advances on 16 February 2022 under the title Experimental evidence for long-distance electrodynamic intermolecular forces with DOI 10.1126/sciadv.abl5855.

The Science Advances paper lists many coauthors and cross-disciplinary contributions, while the LINkS communication and subsequent press material included quotes from project leaders. For example Jérémie Torrès described the experiments as combining a very sensitive setup with a mechanism that produces absorption stronger than water because of collective dipole moments. Marco Pettini suggested the result will require extending standard lists of intermolecular interactions in textbooks and may be paradigm shifting for biophysics.

Caveats, open questions and critical appraisal

The LINkS results are intriguing and are framed as a proof of principle in vitro. They do not by themselves demonstrate that the same mechanism operates in living cells. Several caveats bear emphasis and will guide how the community interprets the claims and plans follow-up work.

In short, the paper provides experimental observations that align with particular theoretical predictions about resonant electrodynamic interactions. Those observations are not yet a definitive demonstration that such forces play a functional role in cells. The authors acknowledge these limitations and call for further work to identify physiological energy sources, to test selectivity among different molecular species and to probe behaviour in crowded and heterogeneous biological environments.

Potential implications and realistic timescales

If long-range electrodynamic forces between biomolecules can be robustly demonstrated and shown to operate under physiological conditions, the implications would be broad. They could change how researchers think about molecular recruitment and encounter rates in crowded cellular environments. Possible applied consequences include new strategies for drug design that exploit long-range complementarity, or for technologies that control molecular associations with light in optogenetic-like approaches. However, translating a laboratory proof of principle into concrete biomedical or technological applications typically requires many additional validation steps, mechanistic dissection, and engineering development that could take years to decades.

What this means for EU research policy and the EIC

LINkS is an example of the kind of high-risk, potentially high-reward science the EIC Pathfinder and related EU mechanisms are designed to support. The research combined physics, biophysics and engineering across multiple institutions and used bespoke instrumentation to address a long-standing theoretical question. Such cross-disciplinary, exploratory projects are resource intensive and uncertain but can open new scientific directions if the results are validated and extended.

From a policy standpoint continued investment in risky fundamental research must be balanced with mechanisms that ensure rigorous peer review, reproducibility checks and open data to accelerate independent verification. Equally, if subsequent studies confirm cellular relevance, translation toward diagnostics, drug discovery and sensing will require different funding instruments and stronger partnerships with industry.

Next steps recommended

Priority follow-up actions are clear. Other groups should attempt independent replications using different proteins, different labels and different measurement platforms. Experiments should probe combinations of molecular species to test selectivity and examine whether ED coupling can occur between nonresonant partners. Work is also needed to establish the energy budgets and dynamics of potential in-cell pumping mechanisms and to measure whether the predicted 1/〈r〉3 scaling persists in crowded, heterogeneous media. Open release of raw data and instrument designs will help accelerate this verification process.

LINkS has reported a stimulating set of observations at the interface of physics and biology. The results merit close attention and rigorous follow-up. Careful replication and critical testing in cell-like environments will determine whether these electrodynamic interactions are a laboratory curiosity or a new piece in the puzzle of biomolecular organisation.