Tianqi Wang

Biocompatible integration of synthetic materials with living tissue remains a major challenge for bioelectronics. In this case, substrate-free conducting polymer (CP) interfaces could help bridge this gap. We report in vivo assembly of n-doped poly(benzodifurandione) (n-PBDF) using whole blood–catalyzed polymerization in awake zebrafish and mice. This approach leverages endogenous catalysts, specifically hemoproteins, to form stable, thermally and ionically sensitive CP networks, ensuring long-term compatibility throughout the lifespan. We showcase the impact of this interface through reversible, cellular, and subcellular neuromodulation using near-infrared (NIR) light, including in vivo polymerized n-PBDF. Electrophysiological studies confirmed that n-PBDF alters intrinsic sodium ion channel excitability, and NIR light stimulation amplifies this modulation through thermoionic-induced shunting, providing on-demand, millisecond-scale reversible inhibitory control of excitability, a feature recapitulated in actively behaving mice.

Potassium channels control membrane potential and various physiological processes, including cell migration. However, the specific role of inwardly rectifying potassium channels in immune cell chemotaxis remains unknown. Here, we demonstrate that inwardly rectifying potassium channels, particularly Kir7.1 (Kcnj13), maintain the resting membrane potential and are crucial for directional sensing during neutrophil chemotaxis. Blocking or knocking out Kir in neutrophils disrupted their ability to sense direction toward different chemoattractants in multiple models. Using genetically encoded voltage indicators, we observed oscillating hyperpolarization during tail retraction in zebrafish neutrophils, with Kir7.1 required for depolarization toward the chemokine source. Focal depolarization via optogenetics biased pseudopod selection and triggered new protrusions, which depended on Gα signaling. Global hyperpolarization caused neutrophils to stall migration. Additionally, Kir influences GPCR signaling activation in dHL-60 cells. This research introduces membrane potential as a key component of the complex feedforward mechanism that links the adaptive and excitable networks necessary to guide immune cells in challenging tissue environments.