Cooperative Ligand-Mediated Transitions in Simple Macromolecules.

Area of Science:

• Synthetic biology
• Chemical engineering
• Biophysics

Background:

• Ligand-mediated transitions (LMT) are crucial in biology, enabling receptor conformational changes upon ligand binding.
• Synthetic systems rarely exhibit sharp, cooperative transitions due to challenges in programming defined conformational states.
• Understanding LMT mechanisms in synthetic systems can inform the design of novel biomimetic materials.

Purpose of the Study:

• To design and investigate synthetic macromolecules exhibiting cooperative ligand-mediated transitions.
• To explore the role of external constraints, specifically immiscible liquids, in controlling macromolecular conformation.
• To elucidate the coupling mechanism between ligand binding and conformational changes in synthetic systems.

Main Methods:

• Utilized two immiscible liquids to create an external constraint on macromolecular conformational states.
• Studied hydrophobic polyelectrolytes (HPE) with ionizable functional groups for proton and hydroxyl ligand binding.
• Investigated oligomeric metal chelators (OMC) that form cross-linked networks upon metal ion binding.

Main Results:

• Observed cooperative transitions in both HPE and OMC systems as a function of ligand concentration.
• Demonstrated that ligand binding and conformational changes are coupled, similar to biological LMT.
• Found that ligand-macromolecule interactions drive cooperativity in HPE, while coordinated bonds enhance cooperativity in OMC.

Conclusions:

• Synthetic macromolecules can be engineered to display cooperative ligand-mediated transitions.
• External constraints, like immiscible liquids, are effective in programming defined conformational states.
• The study provides insights into designing synthetic systems that mimic complex biological processes, with OMC showing enhanced cooperativity.