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Dissolved proteins reverse drift direction when water warms

A mathematical model of thermal diffusion shows that temperature changes across a liquid can explain why dissolved molecules switch direction without needing complex chemical forces.

By Primary News Team

23 statements added · 30 Sep see what was added
Dissolved proteins reverse drift direction when water warms
Source: ArkhipovSergey (CC BY-SA 4.0)
Published30 Sep 2026, 15:06 Last updated30 Sep 2026, 15:06 Sources
Source mode Marks each sentence drawn from a source or a contributor

When a fluid experiences an uneven temperature, microscopic particles suspended within it do not remain evenly distributed. Instead, proteins and colloids drift systematically toward warmer or colder areas, a transport phenomenon known as thermophoresis or the Ludwig-Soret effect.12 For decades, biophysicists have observed that even simple proteins can abruptly reverse their drift direction when the surrounding water warms by only a few degrees, yet explaining why that flip happens has proved difficult.

Understanding how biomolecules move under thermal gradients matters across chemistry and biology. Microscopic temperature differences govern analytical separation techniques in biotechnology laboratories and influence how macromolecules organise within living cells. If scientists can predict which way a particle travels along a temperature gradient, they can design more reliable tools to concentrate molecules, purify pharmaceuticals, and separate cellular fragments.

The underlying sequence of events begins with thermal motion. In warmer water, molecules move more quickly and collide with suspended particles with greater vigour. In cooler water, molecular agitation subsides. Because the viscosity of water drops and thermal agitation increases as temperature rises, the rate at which a suspended protein diffuses changes from point to point across the liquid. That spatial variation in diffusion rate produces a persistent imbalance in random molecular collisions, directing the overall drift of the particles.

A theoretical study by Mayank Sharma, Angad Singh, and A. Bhattacharyay, posted on the arXiv preprint server on September 9, 2026, demonstrates that this spatial variation alone can account for the primary temperature patterns seen in experiments.3 The researchers found that a mathematical correction known as Chapman's non-Fickian diffusion current naturally reproduces how the Soret coefficient changes with temperature, including its sign reversal, when proteins drift in water containing weak salt concentrations.1

Why do dissolved proteins change direction across thermal gradients?

Proteins alter their migration direction because the rate of diffusion varies across space when temperature is uneven. Standard diffusion theory, formulated by Adolf Fick in the nineteenth century, assumes that particles drift solely down concentration gradients under a uniform diffusion rate. In 1928, British mathematician Sydney Chapman generalised Albert Einstein's diffusion theory for non-uniform fluids, demonstrating that when a fluid's properties change across space, an additional non-Fickian diffusion current emerges.12 In 1941, Japanese mathematician Kiyosi Itô developed stochastic calculus methods for space-dependent diffusion that yielded the identical non-Fickian current.1

In a thermal gradient, the temperature difference alters the diffusion constant at every point in the liquid.12 According to the preprint by Sharma, Singh, and Bhattacharyay, this non-Fickian current acts alongside the standard Fickian diffusion current.13 The Soret coefficient, which quantifies the magnitude and direction of thermophoretic movement, can transition from negative to positive as the background temperature rises, meaning the protein switches from moving toward warmer liquid to migrating toward colder liquid.

Dissolved proteins reverse drift direction when water warms
Source: Kpwulab

Arijit explained how this sign reversal emerges physically in response to questions from Primary. Arijit said that the drift current traditionally attributed purely to chemical effects actually reflects competing hydrodynamic and diffusive flows. In response to questions from Primary, Arijit noted that the conventionally assumed drift current "actually comprises all the currents other than the Fickian diffusion current."contributed He explained that "flipping of the so-called drift direction at a particular temperature happens as a competition between the non-Fickian diffusion current and the solvation/pressure current in the presence of a temperature gradient."contributed When temperature climbs, the balance between these two flows shifts, flipping the net direction in which dissolved particles travel.

Mayank Sharma similarly identified spatial diffusivity as a candidate mechanism for this transition. Sharma told Primary that "the work provides a new theoretical perspective and a plausible explanation for Soret's coefficient sign reversal by showing how spatially varying diffusivity plays an important role in inhomogeneous systems."contributed Sharma described the proposed mechanism as "a strong mechanistic candidate" for understanding why the direction flips.contributed

How closely does the model match experimental measurements?

Calculations from the mathematical model align closely with published experimental measurements for three distinct polypeptides in aqueous solutions.13 The authors tested their framework against temperature-dependent Soret coefficient data for the globular enzyme lysozyme, the milk protein beta-lactoglobulin, and the synthetic polypeptide poly-L-lysine.13 In each case, the theoretical curves captured the characteristic shape and sign reversal of the Soret coefficient across the measured temperature range.

Writing on LinkedIn about the study, Mayank Sharma noted that a consistent physical picture of protein thermophoresis has remained elusive despite decades of investigation.36 Sharma stated that introducing a non-Fickian current on top of a Fickian current naturally captures key experimental features, including temperature dependence and sign reversal, suggesting that thermophoretic transport can emerge fundamentally from spatially varying diffusivity.37 In comments to Primary, Sharma added that "these test cases are representative examples of the general physical mechanism governing protein thermophoresis."contributed Co-author Angad Singh echoed that assessment, telling Primary that "the test cases represent the modern standard of experiments, and the diversity of the behaviours observed really warrants the flexibility provided by the framework."contributed

The choice of test molecules was guided by shared behaviour under steady-state conditions rather than molecular structure. Arijit told Primary that "it is not the structural differences between the test cases we considered that have led us to choose them."contributed Instead, the selection hinged on "the similarity in the nature of the steady-state distributions and the corresponding Soret coefficients that we have taken into account, along with the fact that all these reported experimental results are at weak salt concentrations."contributed The structural details of individual polypeptide chains, Arijit added, will be needed later when researchers attempt to calculate microscopic parameters from first principles.

The study also revealed that the bulk behaviour of the solvent carries much of the explanatory burden. Asked what surprised the authors during the derivations, Arijit said that the known physical characteristics of water explained the subtle features of the curves. "It is how beautifully the known properties of water as a function of temperature can produce all the different and competing current components that was something of a surprise to us," Arijit told Primary, adding that "the explicit inclusion of the temperature- and concentration-dependent non-Fickian current led to the remaining gap being bridged by water properties."contributed

Dissolved proteins reverse drift direction when water warms
Source: Jove

What can the diffusion model tell us, and what remains unknown?

The mathematical framework represents a simplified physical model rather than an exhaustive microscopic accounting of every chemical interaction. The calculations assume dilute colloidal suspensions in water with weak salt concentrations, leaving open how high ionic strengths or crowded cellular environments might alter the balance of currents.1 The authors emphasize that while the non-Fickian current is an indispensable element, it works in tandem with local solvation forces, which describe how water molecules and ions physically pack around the protein surface.1 Detailed molecular interactions between the protein surface and surrounding water molecules remain to be fully resolved.1 Furthermore, the findings are posted on a preprint server and have not yet undergone peer review.

Addressing the boundary where this picture holds, Arijit cautioned against extending the minimal model into crowded or chemically aggressive conditions without additional physics. Arijit told Primary that "thermophoresis is a very complex problem in the presence of many competing factors, and we have not reported on other complex situations that could involve varied solvation mechanisms under strong electrostatic forces and solvent conditions."contributed In the three benchmark polypeptides, the researchers did not need to incorporate specialized surface hydration layers because local pressure gradients accounted for the non-diffusive drift. However, Arijit acknowledged that in other physical systems, scientists may need to analyse "the hydration layer and its physics to account for local stresses along the interface, where the pressure-gradient picture is not found adequate."contributed

Evaluating how the framework behaves in concentrated mixtures, Mayank Sharma told Primary that "the balance of currents is expected to remain intact, although increasing ionic strength or cellular crowding may modify the form of solvation force."contributed Singh offered a more guarded view on whether the formulation can survive crowded biological conditions. Singh told Primary that "certainly the framework would struggle in those scenarios, but we won't know the details of what fails, until there is a bigger collection of experimental observations."contributed Sharma also noted that verifying these individual components in the laboratory remains an obstacle. Asked about isolating fluid gradients from surface effects, Sharma told Primary that "separating the two contributions experimentally is challenging."contributed

What happens next in testing non-Fickian transport?

Future experiments will need to probe where diffusion currents end and interfacial forces begin. Arijit stated that non-Fickian diffusion remains "an indispensable element of such processes in the presence of temperature gradients, so long as the diffusion remains indispensable."contributed He noted that in scenarios where solvation forces dominate heavily, such as cases where the steady-state concentration distribution does not display a distinct peak, interfacial chemistry could overshadow diffusion effects. Separating those relative contributions, Arijit said, will require precise new measurements of transport at both single-particle and multi-particle scales.

Assessing how far this perspective diverges from existing theory, Mayank Sharma emphasized that the framework reshapes rather than discards previous work.3 Sharma told Primary that "it is a significant shift in perspective, rather than a complete departure from the standard view."contributed While conventional models focus primarily on complex surface boundaries, Sharma observed that "in systems with negligible electrostatic effects and low salt concentrations, the solvation interactions can be represented through an effective coarse-grained force, with diffusivity gradients governing an important role to thermophoretic transport."contributed

Singh noted that exploring diffusion alone is a necessary initial step before turning to more intricate chemical interactions. Singh told Primary that "it's a departure in the important sense that the effect of varying diffusivity by itself produces a non-trivial distribution. These need to be explored and studied before adopting more complicated forces, in order to get a clearer understanding of the relevance of different effects."contributed

By establishing that space-dependent diffusion can reproduce direction reversal on its own, the study offers a clearer baseline for soft-matter physics. Researchers investigating thermal separation can now determine how much of a molecule's drift stems from classical fluid diffusion before invoking specialized chemical forces.

What this rests on

34 sentences trace to 5 sources and 3 contributors.

  1. 1 MS Mayank Sharma, Angad Singh, A. Bhattacharyay Paper · arxiv.org · 9 Sep 2026 A model of thermophoresis of colloidal proteins in water using non-Fickian diffusion currents Preprint · may not have been peer reviewed See the source
  2. 2 A ar5iv.labs.arxiv.org Paper · ar5iv.labs.arxiv.org Einstein’s random walk and thermal diffusion Preprint · may not have been peer reviewed See the source
  3. 3 L linkedin.com Third-party reporting · linkedin.com · 5 Feb 2026 🔭The plant cuticle has been traditionally believed to be a continuous lipophilic layer covering most aerial plant surfaces, but recent methodological advances based on Atomic Force Microscopy (AFM)… | Physiologia Plantarum See the source
  4. 4 A Arijit Contributor · interview 12–13 Sep 2026 · in the article since 30 Sep 2026 Contribution — Arijit 12 statements added to this article
  5. 5 MS Mayank Sharma Contributor · interview 29 Sep 2026 · in the article since 30 Sep 2026 Contribution — Mayank Sharma 8 statements added to this article
  6. 6 L linkedin.com Third-party reporting · linkedin.com · 1 Feb 2026 Magnetic Fields Affect Biology Despite Weak Strengths | Quantum Biology DAO posted on the topic | LinkedIn See the source
  7. 7 L linkedin.com Third-party reporting · linkedin.com · 21 Jan 2026 Luminescent Lanthanide Metal–Organic Frameworks for Temperature Sensing in Two Distinct Temperature Regions | Stephane Petoud See the source
  8. 8 AS Angad Singh Contributor · interview 30 Sep 2026 · in the article since 30 Sep 2026 Contribution — Angad Singh 3 statements added to this article

Article history

  1. Published 30 Sep 2026, 15:06
    Assembled by the Primary desk from 5 sources · 3 contributors · 34 cited sentences
  2. Angad Singh 3 statements added the day before publication
    1. Go to the sentence: Co-author Angad Singh echoed that assessment, telling Primary that "the test cases represent the modern standard of experiments, and the diversity of the behaviours observed really warrants the flexibility provided by the framework."
    2. Go to the sentence: Singh told Primary that "certainly the framework would struggle in those scenarios, but we won't know the details of what fails, until there is a bigger collection of experimental observations."
    3. Go to the sentence: Singh told Primary that "it's a departure in the important sense that the effect of varying diffusivity by itself produces a non-trivial distribution. These need to be explored and studied before adopting more complicated forces, in order to get a clearer understanding of the relevance of different effects."
  3. Mayank Sharma 8 statements added 2 days before publication
    1. Go to the sentence: Sharma told Primary that "the work provides a new theoretical perspective and a plausible explanation for Soret's coefficient sign reversal by showing how spatially varying diffusivity plays an important role in inhomogeneous systems."
    2. Go to the sentence: Sharma described the proposed mechanism as "a strong mechanistic candidate" for understanding why the direction flips.
    3. Go to the sentence: In comments to Primary, Sharma added that "these test cases are representative examples of the general physical mechanism governing protein thermophoresis."
    4. Go to the sentence: Evaluating how the framework behaves in concentrated mixtures, Mayank Sharma told Primary that "the balance of currents is expected to remain intact, although increasing ionic strength or cellular crowding may modify the form of solvation force."
    5. Go to the sentence: Asked about isolating fluid gradients from surface effects, Sharma told Primary that "separating the two contributions experimentally is challenging."
    6. Go to the sentence: Assessing how far this perspective diverges from existing theory, Mayank Sharma emphasized that the framework reshapes rather than discards previous work.
    7. Go to the sentence: Sharma told Primary that "it is a significant shift in perspective, rather than a complete departure from the standard view."
    8. Go to the sentence: While conventional models focus primarily on complex surface boundaries, Sharma observed that "in systems with negligible electrostatic effects and low salt concentrations, the solvation interactions can be represented through an effective coarse-grained force, with diffusivity gradients governing an important role to thermophoretic transport."
  4. Arijit 12 statements added 18 days before publication
    1. Go to the sentence: The researchers found that a mathematical correction known as Chapman's non-Fickian diffusion current naturally reproduces how the Soret coefficient changes with temperature, including its sign reversal, when proteins drift in water containing weak salt concentrations.
    2. Go to the sentence: In response to questions from Primary, Arijit noted that the conventionally assumed drift current "actually comprises all the currents other than the Fickian diffusion current."
    3. Go to the sentence: He explained that "flipping of the so-called drift direction at a particular temperature happens as a competition between the non-Fickian diffusion current and the solvation/pressure current in the presence of a temperature gradient."
    4. Go to the sentence: Arijit told Primary that "it is not the structural differences between the test cases we considered that have led us to choose them."
    5. Go to the sentence: Instead, the selection hinged on "the similarity in the nature of the steady-state distributions and the corresponding Soret coefficients that we have taken into account, along with the fact that all these reported experimental results are at weak salt concentrations."
    6. Go to the sentence: "It is how beautifully the known properties of water as a function of temperature can produce all the different and competing current components that was something of a surprise to us," Arijit told Primary, adding that "the explicit inclusion of the temperature- and concentration-dependent non-Fickian current led to the remaining gap being bridged by water properties."
    7. Go to the sentence: The calculations assume dilute colloidal suspensions in water with weak salt concentrations, leaving open how high ionic strengths or crowded cellular environments might alter the balance of currents.
    8. Go to the sentence: The authors emphasize that while the non-Fickian current is an indispensable element, it works in tandem with local solvation forces, which describe how water molecules and ions physically pack around the protein surface.
    9. Go to the sentence: Detailed molecular interactions between the protein surface and surrounding water molecules remain to be fully resolved.
    10. Go to the sentence: Arijit told Primary that "thermophoresis is a very complex problem in the presence of many competing factors, and we have not reported on other complex situations that could involve varied solvation mechanisms under strong electrostatic forces and solvent conditions."
    11. Go to the sentence: However, Arijit acknowledged that in other physical systems, scientists may need to analyse "the hydration layer and its physics to account for local stresses along the interface, where the pressure-gradient picture is not found adequate."
    12. Go to the sentence: Arijit stated that non-Fickian diffusion remains "an indispensable element of such processes in the presence of temperature gradients, so long as the diffusion remains indispensable."