Conformational Transduction Amplification in a Biomimetic Polyelectrolyte for Ultrasensitive Imaging of Iron Metabolism

ABSTRACT Proteins exert sophisticated functions through stimulus‐responsive conformational changes. Mimicking this structural control and functional integration in synthetic, water‐soluble polymers has been a fundamental challenge, largely due to the conflict between charge repulsion and conformational order. Here, we report a peptidomimetic polyelectrolyte that overcomes this limitation, maintaining stable and well‐defined helical and sheet‐like conformations across the entire physiological pH range despite its high charge density. This intrinsic conformational order creates through‐space conjugated carbonyl clusters that function as non‐classical chromophores, enabling excitation‐dependent near‐infrared fluorescence with an exceptionally large Stokes shift. More importantly, the sheet‐like conformation enables cooperative, multidentate chelation of Fe 3 + ions, which triggers an allosteric transition to a helix and results in nonlinear and ultrasensitive fluorescence quenching. Leveraging this unique “conformational transduction amplification” mechanism, we achieve real‐time visualization and tracking of iron ion distribution and metabolic pathways at subcellular and whole‐organism levels. This work establishes a paradigm of allosteric control in synthetic polyelectrolytes, opening avenues for the design of intelligent biomimetic materials for advanced sensing and imaging.