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Part 2: Non‐equilibrium polymerization of Amyloid peptides

Mr. Ghosh is currently a PhD student in the lab of Dr. Dibyendu Das (Swarnajayanti Fellow 2020) at the Department of Chemical Sciences, IISER Kolkata. He published a paper titled “Non‐Equilibrium Polymerization of Cross‐β Amyloid Peptides for Temporal Control of Electronic Properties” as a joint first author in Angewandte Chemie International Edition (2020).


Author Interview

How would you explain your paper’s key results to the non-scientific community?

Our work introduces a new class of soft nanomaterials using non-equilibrium amyloid polymerization. You might have heard of Alzheimer’s disease—one of its causes is the abnormal deposition of β-amyloid peptides in the brain. Inspired by how these peptides assemble, we used a small part of the peptide sequence (KLVFFAE) and modified it slightly to HLVFFAE, replacing lysine with histidine.

Our goal was to create a system that could self-assemble and then disassemble on its own, without external triggers. When this short peptide is chemically activated (by coupling with para-nitrophenol), it forms transient cross β-amyloid networks, creating a temporary, structured state that breaks down over time—mimicking a negative feedback loop.


“[…] first to show a closer resemblance with the microtubule formation through a minimalistic peptide sequence acting as self-assembling building blocks.”


What are the possible consequences of these findings for your research area?

We aim to design systems that autonomously organize and break down, mimicking natural systems like microtubules, which constantly assemble and disassemble within cells. Our work marks a stepping stone in this direction.

By leveraging hydrophobic interactions in peptide sequences, we transiently reached a non-equilibrium state. Using various techniques (spectroscopy, microscopy), we observed that the assembled state also acted as a catalyst, helping degrade the chemical fuel that originally triggered the assembly.

Most intriguingly, our temporarily formed networks showed peak conductivity when in their non-equilibrium state—due to tight packing of aromatic residues. This could be useful for developing biosensors, smart materials, or drug delivery systems that operate only during specific time windows.


What was the exciting moment (eureka moment) during your research?

A true eureka moment came when we observed the binding and unbinding behavior of Congo Red dye with our peptide network. This dye is a classic tool used to detect amyloid assemblies.

Our designed peptide bound strongly with Congo Red during its assembled state (seen as a red shift in absorption) and lost the binding as the structure disassembled (seen as a blue shift). This validated our hypothesis beautifully, confirming that we created a transient amyloid system that functions and fades with time—just as designed.


What do you hope to do next?

We plan to further explore peptide-based nanostructures for their diverse structural and functional properties. Our current focus is to study the catalytic properties of these peptides and understand how their design influences their behavior—paving the way for smart, functional materials.


Where do you seek scientific inspiration?

The universe itself is my greatest inspiration. From atoms to galaxies, the quest for truth and understanding drives me. My scientific journey, though limited in scope, is fueled by a deep curiosity to explore the unknown. The effort to uncover hidden mechanisms of nature continues to fascinate and motivate me.


“The scientist is not a person who gives the right answers, he is one who asks the right questions.”


How do you intend to help Indian science improve?

I’ve been privileged to pursue my PhD at IISER Kolkata under the mentorship of Dr. Dibyendu Das. As systems chemists, we strive to create artificial systems inspired by nature. True progress comes not just from finding answers but from asking the right questions—ones that matter to both scientists and the larger society.

By addressing fundamental scientific problems that intersect with real-world applications, I hope to contribute meaningfully to Indian science, fostering innovation and interdisciplinary growth.


Reference

Bal S#, Ghosh C#, Ghosh T, Vijayaraghavan R K, Das D.
Non‐Equilibrium Polymerization of Cross‐β Amyloid Peptides for Temporal Control of Electronic Properties. Angew. Chem. Int. Ed. 2020, 59, 13506. #Equal contribution.


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