Stepwise disassembly of supramolecular structures triggered by specific protein binding.

Area of Science:

• Supramolecular chemistry
• Materials science
• Biomedical engineering

Background:

• Amphiphilic polymers self-assemble into nanostructures for sensing and delivery.
• Peptide-based polymer P1, with hydrophobic M1 and hydrophilic M2/M3 chains, binds bovine carbonic anhydrase II (bCA-II).

Purpose of the Study:

• To understand the assembly/disassembly mechanism of P1 using coarse-grained modeling.
• To investigate the role of bCA-II binding in triggering disassembly.

Main Methods:

• Developed a coarse-grained modeling framework.
• Simulated the dynamic polymer-unimer equilibrium of amphiphilic peptide nanoassembly.
• Introduced bCA-II to simulate its binding and effect on P1 aggregates.

Main Results:

• P1 self-assembles into micelles, which aggregate into larger multicore nanostructures with persistent micelle architecture.
• bCA-II binding initiates stepwise disassembly, first replacing micelle-micelle interfaces with micelle-water interfaces.
• Complete disassembly and cargo release (DiI dye) occur upon multiple bCA-II bindings per micelle.

Conclusions:

• The stepwise disassembly mechanism highlights the balance between stability and responsiveness in supramolecular assemblies.
• Findings offer insights for designing smart materials for biomedical applications, including responsive drug delivery and biosensors.
• Controlled disassembly via specific molecular interactions enables new possibilities for advanced materials.