Author interview — Malay Mondal completed BSc in Biochemistry and Molecular Biology at University of Chittagong, Bangladesh. He did MSc in Biotechnology at South Asian University, New Delhi, India.
- Demonstrates redox-sensitive phase separation via disulfide bonds.
- Highlights cysteine’s role as a tunable cross-linker in LLPS.
- Provides insights for designing redox-responsive, viscoelastic soft materials.
Disulfide bond cross-links can reversibly tune the properties of biomolecular condensates to modulate their percolation behavior.
– Dr. Vijay Rangachari
Our research uncovers the unique role of cysteine residues in controlling the formation and behavior of biomolecular condensates, which are membraneless compartments within cells. Using a simple peptide design, we showed that cysteine’s ability to form reversible disulfide bonds acts as a “tunable switch” for phase separation, a process critical to organizing cellular components. This redox-sensitive mechanism allows the condensates to assemble and disassemble in response to environmental changes, like oxidative stress.
A key finding is that cysteines reduce the threshold concentration required for condensate formation while maintaining fluid-like properties over time. By varying cysteine placement and composition in peptides, we observed subtle but impactful changes in the viscosity and stability of the condensates. Our study also highlights the ability of these structures to adapt and recover through redox cycles, providing insights into their potential biological and material science applications.
This research is novel because it identifies cysteines as dynamic cross-linkers, distinct from conventional models of biomolecular interaction. The findings pave the way for designing smart, redox-responsive materials that mimic biological systems, offering applications in biotechnology, medicine, and sustainable materials engineering. It also enhances our understanding of cellular processes affected by redox chemistry, with potential implications in disease research.
Reference: Reversible Disulfide Bond Cross-Links as Tunable Levers of Phase Separation in Designer Biomolecular Condensates. Malay Mondal et al. J. Am. Chem. Soc. 2024, 146, 36, 25299–25311
