Active Controlled and Tunable Coacervation Using Side-Chain Functional α-Helical Homopolypeptides

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Biophysics

Background:

• Intrinsically disordered proteins (IDPs) are known to form coacervate phases, crucial for cellular organization.
• The molecular determinants governing coacervation in IDPs are complex and challenging to deconvolve.
• Ordered protein structures, like alpha-helices, are generally not expected to form coacervates.

Purpose of the Study:

• To design and synthesize novel alpha-helical homopolypeptides capable of reversible coacervation.
• To investigate the control of coacervation using stimuli-responsive side-chain functionalization.
• To establish a well-defined platform for understanding the fundamental principles of biopolymer coacervation.

Main Methods:

• Synthesis of side-chain amino acid-functionalized alpha-helical homopolypeptides.
• Characterization of coacervate phase formation in aqueous media.
• Investigation of stimuli-responsive behavior (redox, pH, temperature, counterions).
• Molecular dynamics simulations to probe structural and dynamic properties.

Main Results:

• Successfully developed alpha-helical homopolypeptides that reversibly form coacervate phases.
• Demonstrated active control over coacervation via redox chemistry and environmental changes.
• Observed biomimetic properties similar to natural coacervate-forming IDPs.
• Molecular dynamics revealed significant side-chain disorder and hydration despite ordered backbones, explaining coacervation ability.

Conclusions:

• Functionalized alpha-helical polypeptides offer a tunable and well-defined system for studying coacervation.
• Side-chain design is critical for controlling coacervate properties and responsiveness.
• These synthetic polypeptides provide a powerful platform for deconstructing coacervation mechanisms and developing new biomaterials.