Mechanistic Understanding of Electronic Conductivity in Biological Structures via High Performance Computing

Multi-heme cytochromes (MHCs) have attracted much interest for use in nanobioelectronic junctions
due to their high electronic conductances. Their charge transport mechanism has puzzled the community
for many years, though experiment and computation now seem to have converged on a consistent picture.

An often overlooked aspect is that the transport mechanism in MHCs depends strongly on how the transport
is induced: in the native biological environment electrons are injected in and ejected from the heme chain
by molecular donors and acceptors that have a redox potential similar to the heme groups. Here, ultrafast
pump-probe transient absorption spectroscopy and molecular simulation have shown that transport is
via heme-to-heme electron hopping[1]. By contrast,in a junction the electron injection and ejection is facilitated
by metallic electrodes with Fermi-levels that can differ substantially from the redox potentials of the heme groups,
here by 1 eV [2]. Recent measurements on dry and aqueous MHC junctions as well as high performance
computing suggested that a off-resonant coherent tunneling mechanism, not hopping, is operative over
surprisingly long distances, up to about 7 nm [3]. We explain the long coherent tunneling distances by (i) a
low exponential distance decay constant for coherent conduction (\beta = 0.2 Å−1), much lower than for biological
electron transfer (\beta = 1.2-1.4 Å−1) (ii) a large density of protein electronic states that electronically couple
to the electrodes, a factor of 10 higher than for typical molecular wires made of small molecules, prolonging the
coherent tunneling regime to distances that exceed those in molecular wires [4].

In my talk I will consolidate this view by presenting new conductance calculations on MHC junctions where the
number of hemes is systematically varied from 1 to 2 to 3 and 4 hemes and multiples of 4-heme protein
chains approaching lengths of several 10 nanometers. I will also compare MHCs with cable bacteria which
exhibit electronic conductances 3-4 orders of magnitudes higher than MHCs [5]. The transport scenario in cable
bacteria is likely to be very different from the one in MHCs and potentially more similar to the one
in highly conductive organic semiconductors or metal-organic frameworks.[6]

[1] J. H. van Wonderen, K. Adamczyk, X. Wu, X. Jiang, S. E. H. and Piper, C. R. Hall, M. J. Edwards, T. A. Clarke,
H. Zhang, L. J. C. Jeuken, I. Sazanovich, M. Towrie, J. Blumberger, S. R. Meech, and J. N. Butt,
“Nanosecond heme-to-heme electron transfer rates in a multiheme cytochrome nanowire reported by a spectrally
unique His/Met ligated heme,” Proc. Nat. Acad. Sci. USA 118, e2107939118, 2021.

[2] Z. Futera, I. Ide, B. Kayser, K. Garg, X. Jiang, J. H. van Wonderen, J. N. Butt, H. Ishii, I. Pecht, M. Sheves, D. Cahen, and J. Blumberger,
``Coherent electron transport across a 3 nm bioelectronic junction made of multi-heme proteins"
J. Phys. Chem. Lett. 11, 9766-9774, 2020.

[3] Z. Futera, X. Wu, J. Blumberger, ``Tunneling-to-Hopping Transition in Multiheme Cytochrome Bioelectronic Junctions"
J. Phys. Chem. Lett. 14, 445−452, 2023.

[4] Van Nguyen, Q.; Frisbie, C. D. Hopping Conductance in Molecular Wires Exhibits a Large Heavy-Atom KKinetic Isotope Effects.
J. Am. Chem. Soc. 143, 2638−2643, 2021.

[5] Jasper R. van der Veen, Stephanie Valianti, Herre S. J. van der Zant, Yaroslav M. Blanter and Filip J. R. Meysman,
``A model analysis of centimeter-long electron transport in cable bacteria" Phys. Chem. Chem. Phys. 26, 3139-3151, 2024.

[6] S. Giannini and J. Blumberger, “Charge transport in organic semiconductors: the perspective from non-adiabatic molecular dynamics,”
Acc. Chem. Res., vol. 55, 819–830, 2022.