Jingcheng Huang

Diffusion of electrons over distances on the order of 100 μm has been observed in crystals of a small tetraheme cytochrome (STC) from Shewanella oneidensis [J. Huang et al. J. Am. Chem. Soc. 142, 10459–10467 (2020)]. Electron transfer between hemes in adjacent subunits of the crystal is slower and more strongly dependent on temperature than had been expected based on semiclassical electron-transfer theory. We here explore explanations for these findings by molecular-dynamics simulations of crystalline and monomeric STC. New procedures are developed for including time-dependent quantum mechanical energy differences in the gap between the energies of the reactant and product states and for evaluating fluctuations of the electronic-interaction matrix element that couples the two hemes. Rate constants for electron transfer are calculated from the time- and temperature-dependent energy gaps, coupling factors, and Franck–Condon-weighted densities of states using an expression with no freely adjustable parameters. Back reactions are considered, as are the effects of various protonation states of the carboxyl groups on the heme side chains. Interactions with water are found to dominate the fluctuations of the energy gap between the reactant and product states. The calculated rate constant for electron transfer from heme IV to heme Ib in a neighboring subunit at 300 K agrees well with the measured value. However, the calculated activation energy of the reaction in the crystal is considerably smaller than observed. We suggest two possible explanations for this discrepancy. The calculated rate constant for transfer from heme I to II within the same subunit of the crystal is about one-third that for monomeric STC in solution.

The ability to redirect electron transport to new reactions in living systems opens possibilities to store energy, generate new products, or probe physiological processes. Recent work by Huang et al. showed that 3D crystals of small tetraheme cytochromes (STC) can transport electrons over nanoscopic to mesoscopic distances by an electron hopping mechanism, making them promising materials for nanowires. However, fluctuations at room temperature may distort the nanostructure, hindering efficient electron transport. Classical molecular dynamics simulations of these fluctuations at the nano‐ and mesoscopic scales allowed us to develop a graph network representation to estimate maximum electron flow that can be driven through STC wires. In longer nanowires, transient structural fluctuations at protein‐protein interfaces tended to obstruct efficient electron transfer, but these blockages are ameliorated in thicker crystals where alternative electron transfer pathways become more efficient. The model implies that more flexible proteinprotein interfaces limit the required minimum diameter to carry currents commensurate with conventional electronics.

Rapid and directed electron transfer (ET) is essential for biological processes. While the rates of ET over 1-2 nanometers in proteins can largely be described by simplified non-adiabatic theory, it is not known how these processes scale to microscopic distances. We generated crystalline lattices of Small Tetraheme Cytochromes (STC) forming well-defined, three-dimensional networks of closely-spaced redox centers that appear to be nearly ideal for multistep ET. Electrons were injected into specific locations in the STC crystals by direct photoreduction and their redistribution was monitored by imaging. The results demonstrate ET over mesoscopic to microscopic (~100 μm) distances through sequential hopping in a biologically-based heme network. We estimate that a hypothetical “nanowire” composed of crystalline STC with a cross-section about 100 cytochromes could support the anaerobic respiration of a Shewanella cell. The crystalline lattice insulates mobile electrons from oxidation by O₂, compared to those in cytochromes in solution, potentially allowing for efficient delivery of current without production of reactive oxygen species. The platform allows direct tests of whether the assumptions based on short-range ET hold for sequential ET over mesoscopic distances. We estimate that the interprotein ET across 6 Å between hemes in adjacent proteins was about 10⁵ s^-1, about 100-fold slower than expectations based on simplified theory. More detailed analyses implied that additional factors, possibly contributed by the crystal lattice, may strongly impact mesoscale ET mainly by increasing the reorganizational energy of interprotein ET, suggesting design strategies for engineering improved nanowires suitable for future bioelectronic materials.