Preparation of Ultrathin and Degradable Polymeric Films by Electropolymerization of 3-Amino-l-tyrosine.

Bioderived polymers are one of many current research areas that promise a sustainable future. Due to their unique properties, the bioderived polymer polydopamine has been in the spotlight over the last decades. Its ability to adhere to virtually any surface and its stability over a wide pH range as well as in several organic solvents make it a suitable candidate for various applications like coatings and biosensors. However, strong light absorption over a broad range of wavelengths and high quenching efficiency limit its uses. Therefore, new bioderived polymers with similar features to polydopamine but without fluorescence quenching properties are highly desirable. Herein, the electropolymerization of a bioderived analog of dopamine, 3-amino-l-tyrosine, is demonstrated. The resulting polymer, poly(amino-l-tyrosine), exhibits several characteristics complementary to or even exceeding those of polydopamine and its analog, polynorepinephrine, rendering poly(amino-l-tyrosine) attractive for the development of sensors and photoactive devices. Cyclic voltammetry, spectro-electrochemistry, and electrochemical quartz crystal microbalance measurements are applied to study the electrodeposition of this material, and the resulting films are compared to polydopamine and polynorepinephrine. Impedance spectroscopy reveals increased ion permeability of poly(amino-l-tyrosine) compared to polydopamine and polynorepinephrine. Moreover, the reduced fluorescence quenching of poly(amino-l-tyrosine) supports its use as coating for biosensors and organic semiconductors.

Fast Light-Driven Motion of Polydopamine Nanomembranes.

The actuation of micro- and nanostructures controlled by external stimuli remains one of the exciting challenges in nanotechnology due to the wealth of fundamental questions and potential applications in energy harvesting, robotics, sensing, biomedicine, and tunable metamaterials. Photoactuation utilizes the conversion of light into motion through reversible chemical and physical processes and enables remote and spatiotemporal control of the actuation. Here, we report a fast light-to-motion conversion in few-nanometer thick bare polydopamine (PDA) membranes stimulated by visible light. Light-induced heating of PDA leads to desorption of water molecules and contraction of membranes in less than 140 µs. Switching off the light leads to a spontaneous expansion in less than 20 ms due to heat dissipation and water adsorption. Our findings demonstrate that pristine PDA membranes are multiresponsive materials that can be harnessed as robust building blocks for soft, micro-, and nanoscale actuators stimulated by light, temperature, and moisture level.

Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation.

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth-associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

Physicochemical and Electrochemical Characterization of Electropolymerized Polydopamine Films: Influence of the Deposition Process.

Polydopamine (PDA) is a synthetic eumelanin polymer which is, to date, mostly obtained by dip coating processes. In this contribution, we evaluate the physical and electrochemical properties of electrochemically deposited PDA films obtained by cyclic voltammetry or pulsed deposition. The obtained PDA thin films are investigated with respect to their electrochemical properties, i.e., electron transfer (ET) kinetics and charge transfer resistance using scanning electrochemical microscopy and electrochemical impedance spectroscopy, and their nanomechanical properties, i.e., Young's modulus and adhesion forces at varying experimental conditions, such as applied potential or pH value of the medium using atomic force microscopy. In particular, the ET behavior at different pH values has not to date been investigated in detail for electrodeposited PDA thin films, which is of particular interest for a multitude of applications. Adhesion forces strongly depend on applied potential and surrounding pH value. Moreover, force spectroscopic measurements reveal a significantly higher percentage of polymeric character compared to films obtained by dip coating. Additionally, distinct differences between the two depositions methods are observed, which indicate that the pulse deposition process leads to denser, more cross-linked films.

Polymer cyclization for the emergence of hierarchical nanostructures.

The creation of synthetic polymer nanoobjects with well-defined hierarchical structures is important for a wide range of applications such as nanomaterial synthesis, catalysis, and therapeutics. Inspired by the programmability and precise three-dimensional architectures of biomolecules, here we demonstrate the strategy of fabricating controlled hierarchical structures through self-assembly of folded synthetic polymers. Linear poly(2-hydroxyethyl methacrylate) of different lengths are folded into cyclic polymers and their self-assembly into hierarchical structures is elucidated by various experimental techniques and molecular dynamics simulations. Based on their structural similarity, macrocyclic brush polymers with amphiphilic block side chains are synthesized, which can self-assemble into wormlike and higher-ordered structures. Our work points out the vital role of polymer folding in macromolecular self-assembly and establishes a versatile approach for constructing biomimetic hierarchical assemblies.

Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.

BACKGROUND AND PURPOSE: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood. Herein we investigated the spatiotemporal changes in the secondary degenerative thalamus after cortical stroke, using targeted transcriptome approach in conjunction with histology and flow cytometry. METHODS: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery in male C57BL6J mice. Neurodegeneration, neuroinflammatory responses, and microglial activation were examined in naive and stroke mice at from poststroke days (PD) 1 to 84, in both ipsilesional somatosensory cortex and ipsilesional thalamus. NanoString neuropathology panel (780 genes) was used to examine transcriptome changes at PD7 and PD28. Fluorescence activated cell sorting was used to collect CD11c+ microglia from ipsilesional thalamus, and gene expressions were validated by quantitative real-time polymerase chain reaction. RESULTS: Neurodegeneration in the thalamus was detected at PD7 and progressively worsened by PD28. This was accompanied by rapid microglial activation detected as early as PD1, which preceded the neurodegenerative changes. Transcriptome analysis showed higher number of differentially expressed genes in ipsilesional thalamus at PD28. Notably, neuroinflammation was the top activated pathway, and microglia was the most enriched cell type. Itgax (CD11c) was the most significantly increased gene, and its expression was highly detected in microglia. Flow-sorted CD11c+ microglia from degenerative thalamus indicated molecular signatures similar to neurodegenerative disease-associated microglia; these included downregulated Tmem119 and CX3CR1 and upregulated ApoE, Axl, LpL, CSF1, and Cst7. CONCLUSIONS: Our findings demonstrate the dynamic changes of microglia after stroke and highlight the importance of investigating stroke network-wide deficits. Importantly, we report the existence of a unique subtype of microglia (CD11c+) with neurodegenerative disease-associated microglia features in the degenerative thalamus after stroke.

Inflammatory Responses in the Secondary Thalamic Injury After Cortical Ischemic Stroke.

Stroke is one of the major causes of chronic disability worldwide and increasing efforts have focused on studying brain repair and recovery after stroke. Following stroke, the primary injury site can disrupt functional connections in nearby and remotely connected brain regions, resulting in the development of secondary injuries that may impede long-term functional recovery. In particular, secondary degenerative injury occurs in the connected ipsilesional thalamus following a cortical stroke. Although secondary thalamic injury was first described decades ago, the underlying mechanisms still remain unclear. We performed a systematic literature review using the NCBI PubMed database for studies that focused on the secondary thalamic degeneration after cortical ischemic stroke. In this review, we discussed emerging studies that characterized the pathological changes in the secondary degenerative thalamus after stroke; these included excitotoxicity, apoptosis, amyloid beta protein accumulation, blood-brain-barrier breakdown, and inflammatory responses. In particular, we highlighted key findings of the dynamic inflammatory responses in the secondary thalamic injury and discussed the involvement of several cell types in this process. We also discussed studies that investigated the effects of blocking secondary thalamic injury on inflammatory responses and stroke outcome. Targeting secondary injuries after stroke may alleviate network-wide deficits, and ultimately promote stroke recovery.

Photocontrolled Dopamine Polymerization on DNA Origami with Nanometer Resolution.

Temporal and spatial control over polydopamine formation on the nanoscale can be achieved by installing an irradiation-sensitive polymerization system on DNA origami. Precisely distributed G-quadruplex structures on the DNA template serve as anchors for embedding the photosensitizer protoporphyrin IX, which-upon irradiation with visible light-induces the multistep oxidation of dopamine to polydopamine, producing polymeric structures on designated areas within the origami framework. The photochemical polymerization process allows exclusive control over polydopamine layer formation through the simple on/off switching of the light source. The obtained polymer-DNA hybrid material shows significantly enhanced stability, paving the way for biomedical and chemical applications that are typically not possible owing to the sensitivity of DNA.

Facile synthesis of ultrasmall polydopamine-polyethylene glycol nanoparticles for cellular delivery.

Very small polydopamine (PDA) polyethylene glycol (PEG) crosslinked copolymer (PDA-PEG) nanoparticles have been prepared following a convenient one-step procedure in aqueous solution. Particle sizes and colloidal stabilities have been optimized by varying PEG in view of chain length and end group functionalities. In particular, amine-terminated PEG3000 [PEG3000(NH2)2] reacted with polydopamine intermediates so that very small, crosslinked PDA-PEG nanoparticles with sizes of less than 50 nm were formed. These nanoparticles remained stable in buffer solution and no sedimentation occurred. Chemical functionalization was straight-forward as demonstrated by the attachment of fluorescent dyes. The PDA-PEG nanoparticles revealed efficient cellular uptake via endocytosis and high cytocompatibility, thus rendering them attractive candidates for cell imaging or for drug delivery applications.

Water-Dispersible Polydopamine-Coated Nanofibers for Stimulation of Neuronal Growth and Adhesion.

Hybrid nanomaterials have shown great potential in regenerative medicine due to the unique opportunities to customize materials properties for effectively controlling cellular growth. The peptide nanofiber-mediated auto-oxidative polymerization of dopamine, resulting in stable aqueous dispersions of polydopamine-coated peptide hybrid nanofibers, is demonstrated. The catechol residues of the polydopamine coating on the hybrid nanofibers are accessible and provide a platform for introducing functionalities in a pH-responsive polymer analogous reaction, which is demonstrated using a boronic acid modified fluorophore. The resulting hybrid nanofibers exhibit attractive properties in their cellular interactions: they enhance neuronal cell adhesion, nerve fiber growth, and growth cone area, thus providing great potential in regenerative medicine. Furthermore, the facile modification by pH-responsive supramolecular polymer analog reactions allows tailoring the functional properties of the hybrid nanofibers in a reversible fashion.

Polymer tube nanoreactors via DNA-origami templated synthesis.

We describe the stepwise synthesis of precise polymeric objects programmed by a 3D DNA tube transformed from a common 2D DNA tile as a precise biotemplate for atom transfer radical polymerization. The catalytic interior space of the DNA tube was utilized for synthesizing a bio-inspired polymer, polydopamine.

Fabrication of Defined Polydopamine Nanostructures by DNA Origami-Templated Polymerization.

A versatile, bottom-up approach allows the controlled fabrication of polydopamine (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been investigated as an adhesive and promising surface coating material. However, the control of dopamine polymerization is challenged by the multistage-mediated reaction mechanism and diverse chemical structures in PD. DNA origami decorated with multiple horseradish peroxidase-mimicking DNAzyme motifs was used to control the shape and size of PD formation with nanometer resolution. These fabricated PD nanostructures can serve as "supramolecular glue" for controlling DNA origami conformations. Facile liberation of the PD nanostructures from the DNA origami templates has been achieved in acidic medium. This presented DNA origami-controlled polymerization of a highly crosslinked polymer provides a unique access towards anisotropic PD architectures with distinct shapes that were retained even in the absence of the DNA origami template.

"Must not their languages be savage and barbarous like them?" Philology, Indian removal, and race science.

This article highlights the federal government's role as a collector and arbiter of scientific knowledge of "the Indian," in projects directed by Lewis Cass, Albert Gallatin, and Henry R. Schoolcraft; examines the linguistic precursor to biological essentialism; demonstrates white philologists' reliance on Native tutors, some of whom also entered scientific and policy debates; and suggests why the federal government began moving toward English-only instruction even as biological notions of race gained ascendance. During the removal debates, Indian languages focused the attention of men of letters, statesmen, and the broader public. Peter S. Du Ponceau and Cass argued over the grammatical character of the "American languages," with the former praising them and the latter attacking those tongues and the "philanthropic" philology. At stake was the future of Indian affairs and inquirers explored Native languages for evidence of Indians' intellectual and moral capacity to be assimilated into U.S. society. In denying that language corresponded to social condition, Du Ponceau suggested that all Indians spoke according to a uniform, unchanging, and unique "plan of ideas." He and other participants in the debate, such as Wilhelm von Humboldt and Schoolcraft, began to define, linguistically, a distinct and fixed "Indian mind." Scholars of the early republic and antebellum era who wish to study scientific definitions of race must come to terms with linguistic ideas, which requires confronting the intercultural encounters, intellectual exchanges, and institutions through which they emerged.