Bioelectronics devices that directly interface with cells and tissue have applications in neural and cardiac stimulation and recording, electroceuticals, and brain machine interfaces for prostheses. The interface between bioelectronic devices and biological tissue is inherently challenging due to the mismatch in both mechanical properties (hard vs soft) and charge carriers (electrons vs ions). In addition to conventional metals and silicon, new materials have bridged this interface, including conducting polymers, carbon‐based nanomaterials, as well as ion‐conducting polymers and hydrogels. This review provides an update on advances in soft bioelectronic materials for current and future therapeutic applications. Specifically, this review focuses on soft materials that can conduct both electrons and ions, and also deliver drugs and small molecules. The future opportunities and emerging challenges in the field are also highlighted.

Amyloid β (Aβ) 42 is an aggregation-prone peptide and the believed seminal etiological agent of Alzheimer's disease (AD). Intermediates of Aβ42 aggregation, commonly referred to as diffusible oligomers, are considered to be among the most toxic forms of the peptide. Here, we studied the effect of the age-related epimerization of Ser26 (i.e., S26s chiral edit) in Aβ42 and discovered that this subtle molecular change led to reduced fibril formation propensity. Surprisingly, the resultant soluble aggregates were nontoxic. To gain insight into the structural changes that occurred in the peptide upon S26s substitution, the system was probed using an array of biophysical and biochemical methods. These experiments consistently pointed to the stabilization of aggregation intermediates in the Aβ42−S26s system. To better understand the changes arising as a consequence of the S26s substitution, molecular level structural studies were performed. Using a combined nuclear magnetic resonance (NMR)-and density functional theory (DFT)-computational approach, we found that the S26s chiral edit induced only local structural changes in the Gly25−Ser26−Asn27 region. Interestingly, these subtle changes enabled the formation of an intramolecular Ser26−Asn27 H-bond, which disrupted the ability of Asn27 to engage in the fibrillogenic side chain-to-side chain H-bonding pattern. This reveals that intermolecular stabilizing interactions between Asn27 side chains are a key element controlling Aβ42 aggregation and toxicity.

The efficient preparation of single-crystalline ionic polymers and fundamental understanding of their structure–property relationships at the molecular level remains a challenge in chemistry and materials science. Here, we describe the single-crystal structure of a highly ordered polycationic polymer (polyelectrolyte) and its proton conductivity. The polyelectrolyte single crystals can be prepared on a gram-scale in quantitative yield, by taking advantage of an ultraviolet/sunlight-induced topochemical polymerization, from a tricationic monomera self-complementary building block possessing a preorganized conformation. A single-crystal-to-single-crystal photopolymerization was revealed unambiguously by in situ single-crystal X-ray diffraction analysis, which was also employed to follow the progression of molecular structure from the monomer, to a partially polymerized intermediate, and, finally, to the polymer itself. Collinear polymer chains are held together tightly by multiple Coulombic interactions involving counterions to form two-dimensional lamellar sheets (1 nm in height) with sub-nanometer pores (5 Å). The polymer is extremely stable under 254 nm light irradiation and high temperature (above 500 K). The extraordinary mechanical strength and environmental stabilityin combination with its impressive proton conductivity (∼3 × 10–4 S cm–1)endow the polymer with potential applications as a robust proton-conducting material. By marrying supramolecular chemistry with macromolecular science, the outcome represents a major step toward the controlled synthesis of single-crystalline polyelectrolyte materials with perfect tacticity.

Bioelectronics focuses on the interface between biological systems and electronics. Most biological systems are soft and wet, while electronics are typically hard and dry. Information in the form of charge is carried by electrons and holes in electronics, while ions and charged molecules are the charge carriers in biological systems. As such, finding the right material for the bioelectronic interface is challenging. Hydrogels are water swollen porous polymer networks and, similarly to biological systems, hydrogels are wet, soft, and ion conducting. These properties make hydrogels an ideal choice for the bioelectronic interface between electronics and biological systems. This review focuses on polyelectrolyte hydrogels, a class of hydrogels that has fixed charges as part of the polymer network. In order to maintain charge neutrality, these charges attract mobile ions of the opposite charge in the water swollen pores. These mobile ions give the hydrogels selective ionic conductivity. Here, it is discussed brief fundamentals of hydrogels, ionic conduction mechanism and optimization of the conductivity, and applications in bioelectronic sensors and mechanical actuators.

Macrocycles that assemble into nanotubes exhibit emergent properties stemming from their low dimensionality, structural regularity, and distinct interior environments. Here, we report a versatile strategy to synthesize diverse nanotube structures in a single, efficient reaction by using a conserved building block bearing a pyridine ring. Imine condensation of a 2,4,6-triphenylpyridine-based diamine with various aromatic

Bioelectronic devices sense or deliver information at the interface between living systems and electronics by converting biological signals into electronic signals and vice-versa. Biological signals are typically carried by ions and small molecules. As such, ion conducting materials are ideal candidates in bioelectronics for an optimal interface. Among these materials, ion conducting polymers that are able to uptake water are particularly interesting because, in addition to ionic conductivity, their mechanical properties can closely match the ones of living tissue. In this review, we focus on a specific subset of ion-conducting polymers: proton (H + ) conductors that are naturally derived. We first provide a brief introduction of the proton conduction mechanism, and then outline the chemical structure and properties of representative proton-conducting natural biopolymers: polysaccharides (chitosan and glycosaminoglycans), peptides and proteins, and melanin. We then highlight examples of using these biopolymers in bioelectronic devices. We conclude with current challenges and future prospects for broader use of natural biopolymers as proton conductors in bioelectronics and potential translational applications.

Proton conductivity is important in many natural phenomena including oxidative phosphorylation in mitochondria and archaea, uncoupling membrane potentials by the antibiotic Gramicidin, and proton actuated bioluminescence in dinoflagellate. In all of these phenomena, the conduction of protons occurs along chains of hydrogen bonds between water and hydrophilic residues. These chains of hydrogen bonds are also present in many hydrated biopolymers and macromolecule including collagen, keratin, chitosan, and various proteins such as reflectin. All of these materials are also proton conductors. Recently, our group has discovered that the jelly found in the Ampullae of Lorenzini- shark’s electro-sensing organs- is the highest naturally occurring proton conducting substance. The jelly has a complex composition, but we proposed that the conductivity is due to the glycosaminoglycan keratan sulfate (KS). Here we measure the proton conductivity of hydrated keratan sulfate purified from Bovine Cornea. PdH x contacts at 0.50 ± 0.11 mS cm -1 , which is consistent to that of Ampullae of Lorenzini jelly at 2 ± 1 mS cm -1 . Proton conductivity, albeit with lower values, is also shared by other glycosaminoglycans with similar chemical structures including dermatan sulfate, chondroitin sulfate A, heparan sulfate, and hyaluronic acid. This observation supports the relationship between proton conductivity and the chemical structure of biopolymers.

Life is built upon closed-loop feedback and regulation systems that maintain a delicate balance of environmental and metabolic conditions that support cellular function. [1] Bioelectronic devices interface electronic devices with biology with potential for sensing and actuation. [2-5] A challenge for bioelectronic devices is translating between ionic and biochemical signals that dominate biology into electronic currents in the devices and vice versa. Iontronics addresses this challenge by modulating ions directly at the device level rather than electron and holes as in traditional semiconductors. [6] Electrophoretic ion pumps mediate the delivery of ions and charged molecules with an induced electric field [7] to treat epilepsy, [6] chronic pain, [8] inflammation, [9] and to actuate movement in plants. [10] In addition, bioprotonic devices can sense and actuate the flow of H þ in field effect transistors (H þ-FETs), [11,12] enzymatic logic gates, [12] and ion channels. [13] A cell's resting potential, V mem , is an electrical control signal that occurs between the interior of the cell and the extracellular environment regulated by ion channels. [14] In nonexcitable cells, [15] V mem affects cell physiology and functions such as proliferation, differentiation, migration, and apoptosis, as well as cell-cell communication and large-scale morphogenesis. [16] Recently, optically actuated