It’s a problem: How do you ensure proper storage of vaccines and other perishable therapies in places with unreliable refrigeration?
A new study by researchers at Hunter College and the Advanced Science Research Center at CUNY Graduate Center may provide an answer. The study shows that simple peptides can mimic a biological process that protects sensitive proteins such as vaccines and therapeutic proteins from environmental stress, and one day could be used to safeguard therapeutic proteins and vaccines.
The study, led by Distinguished Professor of Chemistry at Hunter College Rein Ulijn, the founding director of the CUNY ASRC Nanoscience Initiative, demonstrates how short peptides — just three amino acids long — can undergo liquid to liquid phase separation through drying that enables the peptides to encapsulate proteins, protect them, and release them intact upon rehydration.
The findings, published August 5 in Nature Materials, offer a promising approach to stabilizing biomolecules — potentially without refrigeration.
The study underscores Hunter’s commitment to being an anchor institution offering high-impact research opportunities in the sciences for a diverse student body.
Inspired by how organisms like tardigrades — a micro-animal that lives in harsh climates — survive extreme dehydration, the researchers asked whether they could replicate nature’s strategy using synthetic materials.
“To our surprise, we found that simple tripeptides could form dynamic, reversible structures that protect proteins under stress,” said Ulijn. “This opens possibilities for protein preservation.”
Cells often respond to stress by creating protective compartments through a process known as phase separation. The compartments stabilize vulnerable proteins and can dissolve again when conditions improve. The research team applied the principle to design adaptable peptide-based materials that mimic the process — offering a simple, effective alternative to conventional methods of biomolecular stabilization, which often require added chemicals and subzero temperatures.
A synergistic combination of laboratory experiments and computer simulations helped show the mechanism behind the process. Dhwanit Dave GC ’23, a Hunter College and ASRC-affiliated graduate student and co-first author, explained: “Computer simulations revealed how the peptides interact to form disordered structures and shed light on the surprising mechanism by which these tripeptides create protein-stabilizing assemblies.”
Key findings from the study include:
- Tripeptides can form reversible, disordered assemblies that undergo phase separation upon drying.
- The assemblies solidify into porous microparticles, efficiently encapsulating proteins.
- Upon rehydration, the peptides release their protein cargo with preserved structural integrity.
- The process mimics natural protective mechanisms and provides insight into a new mode of supramolecular material formation.
“This work not only reveals a novel mechanism of peptide self-organization but also introduces a minimalistic material platform for applications in biotechnology,” said Ulijn.
The implications are far-reaching. From vaccine distribution in regions without reliable refrigeration to new classes of smart, responsive materials, the study lays the foundation for practical innovations and more scientific exploration.
The research was supported primarily by the Air Force Office of Scientific Research, co-led by Dr. Ye He, director of the Live Imaging and Bioenergetics Core and research associate professor of the ASRC Neuroscience Initiative with contributions from ASRC, Columbia University, City College of New York and Hunter College collaborators. Other Hunter-affiliated researchers who are named authors of the paper are Mona Tayarani Najjaran GC ’21; Paola Colon-De Leon, a PhD student at Hunter and ASRC, and Assistant Professor Mateusz Marianski.
In 2021, Ulijn, who also is Hunter’s Einstein Professor of Chemistry, was awarded a U.S. Department of Defense’s Vannevar Bush Faculty Fellowship. The fellowship supports top-tier researchers at U.S. universities whose high-risk, high-reward work is strategically important to the Department of Defense. The five-year fellowship provides $3 million to support Ulijn’s work to understand how complex mixtures of molecules acquire functionality, and to repurpose this understanding to create nanotechnology that is inspired by living systems.
