Tharun Selvam Mahendran
PhD Researcher · Biophysics & Bioengineering

Tharun Selvam Mahendran

State University of New York at Buffalo

My research asks how biomolecular condensates — liquid-like compartments that concentrate RNA and protein inside cells — tip from functional to pathological. Using optical tweezers, microfluidics, and bottom-up reconstitution, I showed that condensate microenvironments can enhance RNA percolation and aggregation, and that homotypic RNA clustering drives a liquid-to-solid transition at condensate cores. A parallel line of work demonstrates that decoupling phase separation from fibrillization preserves condensate biochemical activity — a strategy with direct therapeutic implications for ALS, FTD, and related neurodegenerative diseases.

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Nature Communications · 2026
Decoupling Phase Separation and Fibrillization Preserves Activity of Biomolecular Condensates
Mahendran, T.S., Singh, A., Srinivasan, S., …, Parekh, S.H., Banerjee, P.R.
In plain terms

A common amino acid, L-arginine, can stop healthy protein droplets from hardening into toxic fibrils — without dissolving the droplets or disrupting their job.

First page of the Nature Communications paper — journal header, title, author list and abstract.
Page 1 · Nature Communications 2026 · CC BY 4.0
Central findings
  • The thermodynamic forces that drive condensate formation are separable from those that drive their aging into amyloid fibrils.
  • Fibrils nucleate at the condensate interface, and once a condensate hardens it loses its activity in microtubule assembly.
  • The metabolite L-arginine selectively suppresses fibrillization without perturbing phase separation.
  • L-arginine acts by enhancing condensate viscoelasticity — safe metabolites can preserve condensate function.
Nature Comms ↗
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Nature Chemistry · 2025
Homotypic RNA Clustering Accompanies a Liquid-to-Solid Transition Inside the Core of Multi-Component Biomolecular Condensates
Mahendran, T.S., Wadsworth, G.M., Singh, A., Gupta, R., Banerjee, P.R.
In plain terms

Cellular droplets can drive disease-linked RNA into solid clumps — and an engineered RNA ‘antidote’ can dissolve them again.

First page of the Nature Chemistry paper — title, authors and abstract.
Page 1 · Nature Chemistry 2025 · Mahendran et al.
Central findings
  • Homotypic RNA–RNA clustering drives a liquid-to-solid transition in the condensate core, yielding a solid RNA-rich core inside a fluid shell.
  • The core solidifies through RNA percolation — strands knitting into a single network.
  • Timing is set by RNA sequence, secondary structure, and repeat length.
  • A designed antisense oligonucleotide reverses the clustering — a druggable strategy for repeat-expansion disorders.
UB News ↗Phys.org ↗ScienceDaily ↗
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bioRxiv Preprint · 2025
Viscoelasticity and Interface Properties of Multi-Component Condensates Govern Protein Sequestration and Suppression of Amyloid Formation
Mahendran, T.S., Bremer, A., Gui, X., …, Mittag, T., Banerjee, P.R.
In plain terms

Against the textbook view, stress-granule-like droplets may suppress — not seed — the toxic fibrils linked to ALS.

First page of the bioRxiv preprint — title, authors and abstract.
Page 1 · bioRxiv 2025 · CC BY-NC 4.0
Central findings
  • Contrary to the textbook view, condensates delay and suppress fibril formation by sequestering the protein, so most fibrils grow outside the droplets.
  • Interfacial coverage of fibril-forming protein at the droplet surface sets the lag time before fibrils appear.
  • Condensate viscoelasticity — how “gooey” the droplet is — sets how fast protein leaks out to feed fibril growth.
  • The same rules hold for G3BP1 + RNA stress-granule mimics — stress granules may be protective, not crucibles of disease.
bioRxiv ↗
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Frontiers in Aging Neuroscience · 2020
Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics
Mahendran, T.S., Suresh, S.N., Garimella, L., Manjithaya, R.
In plain terms

Even before it forms the tangles seen in Alzheimer’s, soluble Tau protein can jam the cell’s internal delivery system.

First page of the Frontiers in Aging Neuroscience paper — journal header, title, authors and abstract.
Page 1 · Frontiers in Aging Neuroscience 2020 · CC BY 4.0
Central findings
  • Soluble (non-aggregated) 4R0N Tau disrupts endocytic vesicular dynamics before any tangles form.
  • It reshapes the endolysosomal system — RAB5, RAB7 and LAMP1 rise while beclin-1 falls.
  • This links early soluble Tau to impaired intracellular transport and recycling.
  • Implication: Tau can impair cell function at a pre-fibrillar stage of neurodegeneration.
Open Access ↗
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Molecular Cell · 2025
Tunable Metastability of Condensates Reconciles Their Dual Roles in Amyloid Fibril Formation
Das, T., Zaidi, F.K., Farag, M., …, Mahendran, T.S., …, Pappu, R.V., Mittag, T.
In plain terms

Whether protein droplets protect against or seed toxic fibrils comes down to how easily they ‘melt’ — and that property can be tuned in either direction.

First page of the Molecular Cell paper — title, authors, graphical abstract and highlights.
Page 1 · Molecular Cell 2025
Central findings
  • Condensates and fibrils of the A1-LCD protein form through distinct, separable interactions.
  • The interiors of metastable condensates act as sinks that suppress fibril formation.
  • Disease mutations weaken metastability and accelerate fibril formation.
  • Designed mutations that boost metastability rescue the disease-like phenotype.
Molecular Cell ↗
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Science Advances · 2025
ASPL Couples the Assembly of Stress Granules with Their VCP-Mediated Disassembly
Pareek, G., Li, D., Wang, B., …, Mahendran, T.S., …, Banerjee, P.R., Kim, H.J., Kundu, M.
In plain terms

A protein called ASPL links how stress granules are built to how they’re taken apart — a balance whose breakdown is tied to neurodegeneration.

First page of the Science Advances paper — title, authors and abstract.
Page 1 · Science Advances 2025
Central findings
  • ASPL promotes stress-granule assembly by driving condensation of the scaffold protein G3BP1.
  • The same activity primes granules for VCP-mediated disassembly, coupling build-up and breakdown.
  • Disease-linked VCP mutations disrupt this balance, impairing granule turnover.
  • Connects stress-granule dynamics to neurodegenerative disease mechanisms.
Science Advances ↗
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Cell Biomaterials · 2026
Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs
Ney, M., Sirohi, P., Shmidov, Y., …, Mahendran, T.S., …, Banerjee, P.R., Chilkoti, A.
In plain terms

A designer protein shell inspired by cellular droplets shields peptide drugs like GLP-1 through stomach acid — a step toward taking them as a pill instead of an injection.

First page of the Cell Biomaterials paper — title, authors, graphical abstract and highlights.
Page 1 · Cell Biomaterials 2026
Central findings
  • An engineered protein (SynIDP) responds to gut conditions to release cargo in the intestine.
  • Temperature drives droplet formation; pH drives solidification — two independent knobs.
  • Solidification and larger droplets protect cargo from stomach acid.
  • Orally dosed SynIDP-coated GLP-1 lowered weight and blood sugar in mice.
Cell Biomaterials ↗
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01

Research Focus

01
RNA Phase Transitions
Characterizing the thermodynamic and kinetic drivers of RNA condensation, including repeat-expanded RNAs that drive liquid-to-solid transitions linked to ALS and FTD.
02
Biomolecular Condensates
Using optical tweezers, microfluidics, and single-droplet rheology to quantify how condensate microenvironments regulate client recruitment, sequestration, and pathological self-assembly.
03
Decoupling Phase Separation & Fibrillization
Identifying small molecules and strategies that uncouple condensate formation from amyloid fibril nucleation, preserving the functional biochemistry of condensates.
04
Programmable Therapeutics
Engineering condensate behavior for next-generation RNA-based biologics, oral peptide delivery, and programmable biological materials.
02

Selected Publications

Nature Communications · 2026
Decoupling Phase Separation and Fibrillization Preserves Activity of Biomolecular Condensates
Mahendran, T.S., Singh, A., Srinivasan, S., …, Parekh, S.H., Banerjee, P.R.
Nature Communications
2026 → DOI → PDF
Nature Chemistry · 2025
Homotypic RNA Clustering Accompanies a Liquid-to-Solid Transition Inside the Core of Multi-Component Biomolecular Condensates
Mahendran, T.S., Wadsworth, G., Singh, A.S., Gupta, R., Banerjee, P.R.
Nature Chemistry · Media: EurekAlert, Phys.org
2025 → DOI
Molecular Cell · 2025
Tunable Metastability of Condensates Reconciles Their Dual Roles in Amyloid Fibril Formation
Das, T., Zaidi, F., Farag, M., Ruff, K.M., Mahendran, T.S., …, Banerjee, P.R., Pappu, R.V., Mittag, T.
Molecular Cell · Commentary in Cell Chemical Biology
2025 → DOI
Science Advances · 2025
ASPL Couples the Assembly of Stress Granules with their VCP-Mediated Disassembly
Pareek, G., Li, D., Wang, B., …, Mahendran, T.S., …, Banerjee, P.R., Kundu, M.
Science Advances
2025 → DOI → PDF
bioRxiv Preprint · 2025
Viscoelasticity and Interface Properties of Multi-Component Condensates Govern Protein Sequestration and Suppression of Amyloid Formation
Mahendran, T.S., Bremer, A., Gui, X., …, Mittag, T., Banerjee, P.R.
bioRxiv
2025 → DOI → PDF
bioRxiv Preprint · 2025
Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs
Ney, M., Sirohi, P., Shmidov, Y., …, Mahendran, T.S., …, Banerjee, P.R.
bioRxiv
2025 → DOI
Frontiers in Aging Neuroscience · 2020
Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics
Mahendran, T.S., Suresh, S.N., Garimella, L., Manjithaya, R.
Frontiers in Aging Neuroscience
2020 → DOI → PDF
Chemosphere · 2021
Role of Cerium Oxide Nanoparticles in Improving Oxidative Stress and Developmental Delays in Drosophila melanogaster
Sarkar, A., Mahendran, T.S., …, Sahabudeen, S.
Chemosphere
2021 → DOI
Transcription · 2021
Long Noncoding RNAs: Role and Contribution in Pancreatic Cancer
Ramya Devi, K.T., Karthik, D., Mahendran, T.S., Jaganathan, M.K., Hemdev, S.P.
Transcription
2021 → DOI

Full list → Google Scholar  ·  PubMed  ·  bioRxiv

03

About Me

Education
Ph.D. in Biophysics
State University of New York at Buffalo · Dissertation: The Balancing Act of Biomolecular Condensates in Pathological Aggregation · Supervisor: Prof. Priya R. Banerjee
Jan 2021 – May 2026 (Expected)
B.Tech. in Biotechnology
SRM University, Tamil Nadu, India · First class with distinction
Aug 2015 – May 2019
Next Position
Incoming ODBI Innovator Fellow at Princeton University, with a long-term goal of building an independent research group.
Technical Expertise
Optical Tweezers + Microfluidics Flicker Spectroscopy Live-Cell Confocal Imaging Single-Droplet Rheology Particle-Tracking Nanorheology RNA Biochemistry FPLC Protein Purification Phase Diagram Mapping Fluorescence Lifetime Imaging In Vitro Condensation Assays Python / Image Analysis Adobe Illustrator Drosophila & Mouse Models
Selected Recognition
Best Presentation Award
Buffalo RNA Society, USA
2025
Student Research Achievement Award
Biophysical Society, USA
2025
Sigma Xi Companions in Zealous Research Award
Sigma Xi Society, USA
2025
Dissertation Fellowship
State University of New York at Buffalo
2025
Presidential Fellowship
State University of New York at Buffalo
2021
Tharun Selvam Mahendran presenting research
Presentations

Talks & Conferences

FASEB Phase Transitions in Cellular Signaling (Oral)Jan 2026
Buffalo RNA Society Seminar (Oral)Oct 2025
Biophysical Society Mini-Symposium (Invited Talk)Mar 2025
Biophysical Society Annual Meeting (Poster)Feb 2025
GRC on IDPs, Vaud, Switzerland (Poster)Jun 2024
APS March Meeting (Oral)Mar 2024
04

Get in Touch

I am open to exploring new ideas in the bioengineering and translational medicine space. Feel free to reach out.

Email
tharunse [at] buffalo.edu
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Google Scholar
182 Citations
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LinkedIn
Tharun Selvam Mahendran
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ResearchGate
Tharun Selvam Mahendran
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