Electrostatic binding of polyanions using self-assembled multivalent (SAMul) ligand displays - structure-activity...

Area of Science:

• Nanotechnology and Materials Science
• Biochemistry and Molecular Biology
• Computational Chemistry

Background:

• Self-assembled multivalent (SAMul) displays are engineered nanostructures with tunable properties.
• Understanding nanoscale binding selectivity is crucial for designing advanced biomaterials and drug delivery systems.
• Polyanions like heparin and DNA play vital roles in numerous biological processes.

Purpose of the Study:

• To investigate how modifying ligands in SAMul displays affects binding selectivity towards heparin and DNA.
• To elucidate the thermodynamic principles governing the differential binding of polyanions to SAMul systems.
• To explore the implications of tunable electrostatic interfaces for biological control and regulation.

Main Methods:

• Synthesis and characterization of self-assembled multivalent (SAMul) displays with varying ligands.
• Experimental binding assays including competition assays and isothermal calorimetry.
• Multiscale computational modeling to analyze binding thermodynamics and polyanion dynamics.

Main Results:

• Spermidine ligands demonstrated optimal binding to heparin, while spermine ligands were preferred for DNA binding.
• Isothermal calorimetry and competition assays confirmed significant differences in binding affinity and provided thermodynamic insights.
• Multiscale modeling revealed that DNA's shape persistence drives selectivity through ligand preference, whereas heparin's flexibility allows it to reinforce ligand preferences.

Conclusions:

• Inherent differences in polyanion flexibility and shape influence binding selectivity at the nanoscale.
• Ligand modifications in SAMul displays offer a tunable approach to control interactions with specific biomolecules.
• These findings have potential applications in nanoscale biological control, regulation, and the development of targeted therapies.