Transmembrane transport in inorganic colloidal cell-mimics.

A key aspect of living cells is their ability to harvest energy from the environment and use it to pump specific atomic and molecular species in and out of their system-typically against an unfavourable concentration gradient1. Active transport allows cells to store metabolic energy, extract waste and supply organelles with basic building blocks at the submicrometre scale. Unlike living cells, abiotic systems do not have the delicate biochemical machinery that can be specifically activated to precisely control biological matter2-5. Here we report the creation of microcapsules that can be brought out of equilibrium by simple global variables (illumination and pH), to capture, concentrate, store and deliver generic microscopic payloads. Borrowing no materials from biology, our design uses hollow colloids serving as spherical cell-membrane mimics, with a well-defined single micropore. Precisely tunable monodisperse capsules are the result of a synthetic self-inflation mechanism and can be produced in bulk quantities. Inside the hollow unit, a photoswitchable catalyst6 produces a chemical gradient that propagates to the exterior through the membrane's micropore and pumps target objects into the cell, acting as a phoretic tractor beam7. An entropic energy barrier8,9 brought about by the micropore's geometry retains the cargo even when the catalyst is switched off. Delivery is accomplished on demand by reversing the sign of the phoretic interaction. Our findings provide a blueprint for developing the next generation of smart materials, autonomous micromachinery and artificial cell-mimics.

Living materials fabricated via gradient mineralization of light-inducible biofilms.

Living organisms have evolved sophisticated cell-mediated biomineralization mechanisms to build structurally ordered, environmentally adaptive composite materials. Despite advances in biomimetic mineralization research, it remains difficult to produce mineralized composites that integrate the structural features and 'living' attributes of their natural counterparts. Here, inspired by natural graded materials, we developed living patterned and gradient composites by coupling light-inducible bacterial biofilm formation with biomimetic hydroxyapatite (HA) mineralization. We showed that both the location and the degree of mineralization could be regulated by tailoring functional biofilm growth with spatial and biomass density control. The cells in the composites remained viable and could sense and respond to environmental signals. Additionally, the composites exhibited a maximum 15-fold increase in Young's modulus after mineralization and could be applied to repair damage in a spatially controlled manner. Beyond insights into the mechanism of formation of natural graded composites, our study provides a viable means of fabricating living composites with dynamic responsiveness and environmental adaptability.

CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy.

BACKGROUND: Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation. RESULTS: In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage. CONCLUSIONS: The UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.

Dimeric Corrole Analogs of Chlorophyll Special Pairs.

Chlorophyll special pairs in photosynthetic reaction centers function as both exciton acceptors and primary electron donors. Although the macrocyclic natural pigments contain Mg(II), the central metal in most synthetic analogs is Zn(II). Here we report that insertion of either Al(III) or Ga(III) into an imidazole-substituted corrole affords an exceptionally robust photoactive dimer. Notably, attractive electronic interactions between dimer subunits are relatively strong, as documented by signature changes in NMR and electronic absorption spectra, as well as by cyclic voltammetry, where two well-separated reversible redox couples were observed. EPR spectra of one-electron oxidized dimers closely mimic those of native special pairs, and strong through-space interactions between corrole subunits inferred from spectroscopic and electrochemical data are further supported by crystal structure analyses (3 Å interplanar distances, 5 Å lateral shifts, and 6 Å metal to metal distances).

Visible-Light-Promoted Biomimetic Reductive Functionalization of Quaternary Benzophenanthridine Alkaloids.

Reduction of an iminium C═N double bond is the most important phase I metabolism process associated with the cytotoxic property of quaternary benzophenanthridine alkaloids (QBAs). Inspired by the light-mediated reduction of QBAs with nicotinamide adenine dinucleotide, a visible-light-promoted reductive functionalization reaction of QBAs is reported in this study. C4-Alkyl-1,4-dihydropyridines (DHPs) enable the direct reductive alkylation of QBA independently, serving as both single-electron-transfer reductant reagents under irradiation with 455 nm blue light in the absence of photocatalysts and additional additives. Our protocol can be further applied to the semisynthesis of natural 6-substituted dihydrobenzophenanthridine derivatives such as O-acetyl maclekarpine E.

Two-Dimensional Metal-Organic Framework Film for Realizing Optoelectronic Synaptic Plasticity.

2D metal-organic framework (MOF) film as the active layer show promising application prospects in various fields including sensors, catalysis, and electronic devices. However, exploring the application of 2D MOF film in the field of artificial synapses has not been implemented yet. In this work, we fabricated a novel 2D MOF film (Cu-THPP, THPP=5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine), and further used it as an active layer to explore the application in the simulation of human brain synapses. It shows excellent light-stimulated synaptic plasticity properties, and exhibits the foundation function of synapses such as long-term plasticity (LTP), short-term plasticity (STP), and the conversion of STP to LTP. Most critically, the MOF based artificial synaptic device exhibits an excellent stability in atmosphere. This work opens the door for the application of 2D MOF film in the simulation of human brain synapses.

Metal-Organic Framework Membrane Nanopores as Biomimetic Photoresponsive Ion Channels and Photodriven Ion Pumps.

Biological ion channels and ion pumps with sub-nanometer sizes modulate ion transport in response to external stimuli. Realizing such functions with sub-nanometer solid-state nanopores has been an important topic with wide practical applications. Herein, we demonstrate a biomimetic photoresponsive ion channel and photodriven ion pump using a porphyrin-based metal-organic framework membrane with pore sizes comparable to hydrated ions. We show that the molecular-size pores enable precise and robust optoelectronic ion transport modulation in a broad range of concentrations, unparalleled with conventional solid-state nanopores. Upon decoration with platinum nanoparticles to form a Schottky barrier photodiode, photovoltage across the membrane is generated with "uphill" ion transport from low concentration to high concentration. These results may spark applications in energy conversion, ion sieving, and artificial photosynthesis.

Endo- and Exo-Functionalized Tetraphenylethylene M12L24 Nanospheres: Fluorescence Emission inside a Confined Space.

The intrinsic relationship between the properties of green fluorescent protein (GFP) and its encapsulated small molecular light machine has spurred many biomimicking studies, aiming at revealing the detailed mechanism and further promoting its wide applications in different disciplines. However, how to build a similar confined microenvironment to mimic the cavity of a ß-barrel and the fluorescence turn-on process is a fundamental challenge for both chemists and biologists. Herein, two distinct exo- and endo-functionalized tetraphenylethylene (TPE)-based M12L24 nanospheres with precise distribution of anchored TPE moieties and unique photophysical properties were constructed by means of a coordination-driven self-assembly strategy. Under dilute conditions, the nanospheres fluoresce more strongly than the corresponding TPE subcomponents. Meanwhile, the endo-functionalized sphere is able to induce a higher local concentration and more restrained motion of the enclosed 24 TPE units compared with exo-functionalized counterpart and thus induces much stronger emission due to the restriction of the rotation of the pendant TPE units. The biomimetic methodology developed here represents a promising way to understand and construct artificial GFP materials on the platforms of supramolecular coordination complexes.

Rhodopsin-Like Ionic Gate Fabricated with Graphene Oxide and Isomeric DNA Switch for Efficient Photocontrol of Ion Transport.

Rhodopsin, composed of opsin and isomeric retinal, acts as the primary photoreceptor by converting light into electric signals. Inspired by rhodopsin, we have fabricated a light-regulated ionic gate on the basis of the design of a graphene oxide (GO)-biomimetic DNA-nanochannel architecture. In this design, photoswitchable azobenzene (Azo)-DNA is introduced to the surface of porous anodic alumina (PAA) membrane. With modulation of the interaction between the GO blocker and Azo-DNA via flexibly regulating trans and cis states of Azo under the irradiation of visible and ultraviolet light, alternatively, the ionic gate is switched between ON and OFF states. This newly constructed ionic gate can possess high efficiency for the control of ion transport because of the high blocking property of GO and the rather tiny path within the barrier layer which are both first employed to fabricate ionic gate. We anticipate that this rhodopsin-like ionic gate may provide a new model and method for the investigation of ion channel, ion function, and ion quantity. In addition, because of the advantages of simple fabrication, good biocompatibility, and universality, this bioinspired system may have potential applications as optical sensors, in photoelectric transformation, and in controllable drug delivery.

Bayesian inference of a human bone and biomaterials using ultrasonic transmitted signals.

Ultrasonic techniques could be good candidates to aid the assessment of osteoporosis detection, due to their non-intrusiveness and low cost. While earlier studies made use of the measured ultrasonic phase velocity and attenuation inside the bone, very few have considered an inverse identification of both the intrinsic pore microstructure and the mechanical properties of the bone, based on Biot's model. The main purpose of this work is to present an in vitro methodology for bone identification, adopting a statistical Bayesian inference technique using ultrasonic transmitted signals, which allows the retrieval of the identified parameters and their uncertainty. In addition to the bone density, Young's modulus and Poisson's ratio, the bone pore microstructure parameters (porosity, tortuosity, and viscous length) are identified. These additional microstructural terms could improve the knowledge on the correlations between bone microstructure and bone diseases, since they provide more information on the trabecular structure. In general, the exact properties of the saturating fluid are unknown (bone marrow and blood in the case of bone study) so in this work, the fluid properties (water) are identified during the inference as a proof of concept.

Visible Light-Activatable Oxidase Mimic of 9-Mesityl-10-Methylacridinium Ion for Colorimetric Detection of Biothiols and Logic Operations.

In this work, 9-mesityl-10-methylacridinium ion (Acr+-Mes) is found to act as an effective photocatalyst mimicking the function of oxidase. Upon visible light illumination, the excited Acr+-Mes is able to exhibit superior enzymatic catalytic activity for small molecular substrates as well as protein biomacromolecule (cytochrome c). The experiment results demonstrate that the Acr+-Mes oxidase mimic shows higher affinity to 3,3',5,5'-tetramethylbenzidine (TMB) than natural horseradish peroxidase or the reported molecule oxidase mimic. The reaction mechanism is ascribed to the strong oxidation property of the long-lived electron-transfer state (Acr•-Mes•+) and the electron transfer from Acr•-Mes radical to dissolved oxygen to generate superoxide radicals, which can easily oxidize various substrates. On the basis of these observations, the light-activatable Acr+-Mes with an oxidase-like activity as the probe is utilized for cost-effective, sensitive, and highly selective colorimetric detection of two biothiols (L-cysteine and L-glutathione). The lowest detectable concentrations of L-Cys and L-GSH is 100 nM, which is lower than that of most of the reported methods for biothiols. Beyond this, we construct a series of visual molecular logic gates (AND, INH, and NOR) using the oxidase mimic-involved reaction systems.

Photoinduced Intermolecular Electron Transfer Mediated by the Colloidal Tyrosyl Bolaamphiphile Assembly.

The self-assembly of tyrosyl bolaamphiphiles is exploited to create a colloidal protein-like host matrix, upon which sacrificial electron-donor molecules associate to create a photosystem II (PSII) mimetic electron-relay system. This system harnesses the tyrosine phenol groups abundant on the surface of the assemblies to mediate photoinduced intermolecular electron transfer. Compared with the l-tyrosine molecules, the tyrosyl bolaamphiphile assembly facilitates electron transfer from the sacrificial electron donor to the oxidized photosensitizer. The enhanced electron relay is likely to be driven by the host function of the assembly associated with the sacrificial electron donor and by the suppression of the oxidative cross-linking of phenoxyl radicals. The tyrosyl bolaamphiphile assembly is advantageous in the construction of a PSII mimetic system with a protein-like nature and displaying biochemical functions.

Synthesis and characterization of a photocleavable collagen-like peptide.

A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution. Illumination of a thin film of the peptide, or a thin film of a photoreactive amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with femtosecond laser light at 710 nm allows for the creation of well-resolved micropatterns. The cytocompatibility of the peptide was demonstrated using human mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the full-length peptide is cytocompatible as it can support cell growth and maintain cell viability. In contrast, the small peptide fragments created by photolysis are somewhat cytotoxic and therefore less cytocompatible. These data suggest that biomimetic collagen-like photoreactive peptides could potentially be used for growing cells in 2D micropatterns based on patterns generated by photolysis prior to cell growth.

Coherent Exciton Delocalization in a Two-State DNA-Templated Dye Aggregate System.

Coherent exciton delocalization in dye aggregate systems gives rise to a variety of intriguing optical phenomena, including J- and H-aggregate behavior and Davydov splitting. Systems that exhibit coherent exciton delocalization at room temperature are of interest for the development of artificial light-harvesting devices, colorimetric detection schemes, and quantum computers. Here, we report on a simple dye system templated by DNA that exhibits tunable optical properties. At low salt and DNA concentrations, a DNA duplex with two internally functionalized Cy5 dyes (i.e., dimer) persists and displays predominantly J-aggregate behavior. Increasing the salt and/or DNA concentrations was found to promote coupling between two of the DNA duplexes via branch migration, thus forming a four-armed junction (i.e., tetramer) with H-aggregate behavior. This H-tetramer aggregate exhibits a surprisingly large Davydov splitting in its absorbance spectrum that produces a visible color change of the solution from cyan to violet and gives clear evidence of coherent exciton delocalization.

Photosynthetic Proteins in Supported Lipid Bilayers: Towards a Biokleptic Approach for Energy Capture.

In nature, plants and some bacteria have evolved an ability to convert solar energy into chemical energy usable by the organism. This process involves several proteins and the creation of a chemical gradient across the cell membrane. To transfer this process to a laboratory environment, several conditions have to be met: i) proteins need to be reconstituted into a lipid membrane, ii) the proteins need to be correctly oriented and functional and, finally, iii) the lipid membrane should be capable of maintaining chemical and electrical gradients. Investigating the processes of photosynthesis and energy generation in vivo is a difficult task due to the complexity of the membrane and its associated proteins. Solid, supported lipid bilayers provide a good model system for the systematic investigation of the different components involved in the photosynthetic pathway. In this review, the progress made to date in the development of supported lipid bilayer systems suitable for the investigation of membrane proteins is described; in particular, there is a focus on those used for the reconstitution of proteins involved in light capture.

Photocatalysis deconstructed: design of a new selective catalyst for artificial photosynthesis.

A rapid increase in anthropogenic emission of greenhouse gases, mainly carbon dioxide, has been a growing cause for concern. While photocatalytic reduction of carbon dioxide (CO2) into solar fuels can provide a solution, lack of insight into energetic pathways governing photocatalysis has impeded study. Here, we utilize measurements of electronic density of states (DOS), using scanning tunneling microscopy/spectroscopy (STM/STS), to identify energy levels responsible for photocatalytic reduction of CO2-water in an artificial photosynthetic process. We introduce desired states in titanium dioxide (TiO2) nanoparticles, using metal dopants or semiconductor nanocrystals, and the designed catalysts were used for selective reduction of CO2 into hydrocarbons, alcohols, and aldehydes. Using a simple model, we provide insights into the photophysics governing this multielectron reduction and design a new composite photocatalyst based on overlapping energy states of TiO2 and copper indium sulfide (CIS) nanocrystals. These nanoparticles demonstrate the highest selectivity for ethane (>70%) and a higher efficiency of converting ultraviolet radiation into fuels (4.3%) using concentrated sunlight (>4 Sun illumination), compared with platinum-doped TiO2 nanoparticles (2.1%), and utilize hot electrons to tune the solar fuel from alkanes to aldehydes. These results can have important implications for the development of new inexpensive photocatalysts with tuned activity and selectivity.

Light-Driven Multidirectional Bending in Artificial Muscles.

Using light to drive polymer actuators can enable spatially selective complex motions, offering a wealth of opportunities for wireless control of soft robotics and active textiles. Here, the integration of photothermal components is reported into shape memory polymer actuators. The fabricated twist-coiled artificial muscles show on-command multidirectional bending, which can be controlled by both the illumination intensity, as well as the chirality, of the prepared artificial muscles. Importantly, the direction in which these artificial muscles bend does not depend on intrinsic material characteristics. Instead, this directionality is achieved by localized untwisting of the actuator, driven by selective irradiation. The reaction times of this bending system are significantly - at least two orders of magnitude - faster than heliotropic biological systems, with a response time up to one second. The programmability of the artificial muscles is further demonstrated for selective, reversible, and sustained actuation when integrated in butterfly-shaped textiles, along with the capacity to autonomously orient toward a light source. This functionality is maintained even on a rotating platform, with angular velocities of 6°/s, independent of the rotation direction. These attributes collectively represent a breakthrough in the field of artificial muscles, intended to adaptive shape-changing soft systems and biomimetic technologies.

Near-Infrared Responsive Biomimetic Titanate/TiO2-X Heterostructure: A Therapeutic Strategy for Combating Implant-Associated Infection and Enhancing Osseointegration.

Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiation─94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.

Indigenously developed multipurpose acrylic head phantom for verification of IMRT using film and gel dosimetry.

The purpose of this study was to validate the newly designed acrylic phantom for routine dosimetric purpose in radiotherapy. The phantom can be used to evaluate and compare the calculated dose and measured dose using film and gel dosimetric methods. In this study, a doughnut-shaped planning target volume (8.54 cm3) and inner organ at risk (0.353 cm3) were delineated for an IMRT test plan using the X-ray CT image of the phantom. The phantom consists of acrylic slabs which are integrated to form a human head with a hole in the middle where several dosimetric inserts can be positioned for measurement. An inverse planning with nine coplanar intensity-modulated fields was created using Pinnacle TPS. For the film analysis, EBT2 film, flatbed scanner, in-house developed MATLAB codes and ImageJ software were used. The 3D dose distribution recorded in the MAGAT gel dosimeter was read using a 1.5 T MRI scanner. Scanning parameters were CPMG pulse sequence with 8 equidistant echoes, TR = 5600, echo step = 22 ms, pixel size = 0.5 × 0.5, slice thickness = 2 mm. Using a calibration relationship between absorbed dose and spin-spin relaxation rate (R2), R2 images were converted to dose images. The dose comparison was accomplished using in-house MATLAB-based graphical user interface named "IMRT3DCMP". For gel measurement dose grid from the TPS was extracted and compared with the measured dose grid of the gel. Gamma index analysis of film measurement for the tolerance criteria of 2%/2mm, 1%/1 mm showed more than 90% voxels pass rate. Gamma index analysis of 3D gel measurement data showed more than 90% voxels pass rate for different tolerance criteria of 2%/2 mm and 1%/1 mm. Overall both 2D and 3D measurement were in close agreement with the Pinnacle TPS calculated dose. The phantom designed is cost-effective and the results are promising, but further investigation is required to validate the phantom with other 3D conformal techniques for dosimetric purpose.