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bioRxiv · 10.1101/2025.09.10.674898

Condensate-based shells and scaffolds via interfacial liquid-to-solid transition of disordered peptides

Chen, C.·Wang, Q.·Jarnot, N.·Dijkgraaf, I.·Deshpande, S.
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Abstract

Living organisms use biomolecular condensates to respond to dynamic environments and create functional materials with complex architectures. Exploring such phase-separated systems beyond the naturally occurring scenarios may offer valuable insights for emergent synthetic biosystems. Here, we report the self-assembly behavior of a short, disordered peptide sequence (termed CT45) derived from a protein present in the bioad-hesive system of tick ectoparasites. We show that CT45 spontaneously accumulates at polar-nonpolar interfaces, and further undergoes liquid-liquid and liquid-to-solid phase transitions to create mechanically stable structures. When encapsulated within vesicles and presented with a stable oil-water interface, CT45 rapidly forms solid shells, which can be reinforced by up-concentrating the material through osmotic imbalance. Unex-pectedly, when presented with a transient acetone-water interface, CT45 condenses at the evaporating interface and forms interconnected, porous mesoscopic scaffolds. The underlying mechanism is found to be the amphiphilic nature of CT45 leading to in-terfacial accumulation, enhancing intermolecular{pi} -based interactions to trigger phase transitions. The micron-sized shells exhibit appreciable mechanical strength and the porous scaffolds present a highly stable platform capable of retaining molecules. In conclusion, the presented condensate-based microscopic and mesoscopic scaffolds hold significance in customizable condensate architectures, with potential applications in biomedical engineering and synthetic biology.

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Chen, C., Wang, Q., Jarnot, N., Dijkgraaf, I., Deshpande, S.. 2025-09-16. Condensate-based shells and scaffolds via interfacial liquid-to-solid transition of disordered peptides. https://doi.org/10.1101/2025.09.10.674898

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