Enhancement of direct electron transfer in graphene bioelectrodes containing novel cytochrome c553 variants with optimized heme orientation.

The highly efficient bioelectrodes based on single layer graphene (SLG) functionalized with pyrene self-assembled monolayer and novel cytochromec553(cytc553)peptide linker variants were rationally designed to optimize the direct electron transfer (DET) between SLG and the heme group of cyt. Through a combination of photoelectrochemical and quantum mechanical (QM/MM) approaches we show that the specific amino acid sequence of a short peptide genetically inserted between the cytc553holoprotein and thesurface anchoring C-terminal His6-tag plays a crucial role in ensuring the optimal orientation and distance of the heme group with respect to the SLG surface. Consequently, efficient DET occurring between graphene and cyt c553 leads to a 20-fold enhancement of the cathodic photocurrent output compared to the previously reported devices of a similar type. The QM/MM modeling implies that a perpendicular or parallel orientation of the heme group with respect to the SLG surface is detrimental to DET, whereas the tilted orientation favors the cathodic photocurrent generation. Our work confirms the possibility of fine-tuning the electronic communication within complex bio-organic nanoarchitectures and interfaces due to optimization of the tilt angle of the heme group, its distance from the SLG surface and optimal HOMO/LUMO levels of the interacting redox centers.

Molecular mechanism of direct electron transfer in the robust cytochrome-functionalised graphene nanosystem.

Construction of green nanodevices characterised by excellent long-term performance remains high priority in biotechnology and medicine. Tight electronic coupling of proteins to electrodes is essential for efficient direct electron transfer (DET) across the bio-organic interface. Rational modulation of this coupling depends on in-depth understanding of the intricate properties of interfacial DET. Here, we dissect the molecular mechanism of DET in a hybrid nanodevice in which a model electroactive protein, cytochrome c 553 (cyt c 553), naturally interacting with photosystem I, was interfaced with single layer graphene (SLG) via the conductive self-assembled monolayer (SAM) formed by pyrene-nitrilotriacetic acid (pyr-NTA) molecules chelated to transition metal redox centers. We demonstrate that efficient DET occurs between graphene and cyt c 553 whose kinetics and directionality depends on the metal incorporated into the bio-organic interface: Co enhances the cathodic current from SLG to haem, whereas Ni exerts the opposite effect. QM/MM simulations yield the mechanistic model of interfacial DET based on either tunnelling or hopping of electrons between graphene, pyr-NTA-M2+ SAM and cyt c 553 depending on the metal in SAM. Considerably different electronic configurations were identified for the interfacial metal redox centers: a closed-shell system for Ni and a radical system for the Co with altered occupancy of HOMO/LUMO levels. The feasibility of fine-tuning the electronic properties of the bio-molecular SAM upon incorporation of various metal centers paves the way for the rational design of the optimal molecular interface between abiotic and biotic components of the viable green hybrid devices, e.g. solar cells, optoelectronic nanosystems and solar-to-fuel assemblies.

Bone mineral disease in children after renal transplantation in steroid-free and steroid-treated patients--a prospective study.

UNLABELLED: Bone disease may persist after transplantation. Different approaches aiming to ameliorate this problem have been investigated. The aim of the study was to compare the long-term effect of three medical interventions: (i) two prophylactic oral doses of 50 mg ibandronate; (ii) daily oral dose of 0.25 µg of 1α-OHD3 (both of these regimens in patients receiving steroids), and (iii) steroid minimization immunosuppressive protocol in patients with no other specific prophylaxis. PATIENTS: A total of 37 children, at a mean age of 13.33±3.49 yr, dialyzed for 15.93±16.7 months before transplantation, were divided into three groups, depending on medical intervention. Bone mineral content and density (BMC, BMD, DXA), serum markers of bone resorption and formation (CTX, P1NP), calcium, phosphate, 25OHD3/1.25 (OH)2D3 and PTH concentration were evaluated during two yr of follow-up. The mean values of BMD in the whole population and among the three subgroups remained within the age- and gender-matched normal range during follow-up. PATIENTS from groups II (alphacalcidiol) and III (steroid minimization) showed a significant decrease in BMD Z-scores over time, and this effect was determined with increasing age using multivariate analysis. PATIENTS receiving two doses of ibandronate maintained unchanged Z-scores for BMD and BMC over time.