Observation of giant conductance fluctuations in a protein

Abstract

Proteins are insulating molecular solids, yet even those containing easily reduced or oxidized centers can have single-molecule electronic conductances that are too large to account for with conventional transport theories. Here, we report the observation of remarkably high electronic conductance states in an electrochemically-inactive protein, the ~200 kD αVβ3 extracelluar domain of human integrin. Large current pulses (up to nA) were observed for long durations (many ms, corresponding to many pC of charge transfer) at large gap (>5nm) distances in an STM when the protein was bound specifically by a small peptide ligand attached to the electrodes. The effect is greatly reduced when a homologous, weakly-binding protein (α4β1) is used as a control. In order to overcome the limitations of the STM, the time- and voltage-dependence of the conductance were further explored using a fixed-gap (5 nm) tunneling junction device that was small enough to trap a single protein molecule at any one time. Transitions to a high conductance (~ nS) state were observed, the protein being “on” for times from ms to tenths of a second. The high-conductance states only occur above ~ 100mV applied bias, and thus are not an equilibrium property of the protein. Nanoamp two-level signals indicate the specific capture of a single molecule in an electrode gap functionalized with the ligand. This offers a new approach to label-free electronic detection of single protein molecules. Electronic structure calculations yield a distribution of energy level spacings that is consistent with a recently proposed quantum-critical state for proteins, in which small fluctuations can drive transitions between localized and band-like electronic states.

Role of contacts in long-range protein conductance

“…Controls (buffer alone or noncognate proteins in solution) gave no signals. The rapidly fluctuating (millisecond-timescale) telegraph noise (TN) reported (15) for integrin is also observed here for anti-DNP (Fig. 1 C and D ), and all of the other proteins studied ( SI Appendix , Fig.…”

“…3 E and SI Appendix , Figs. S5 and S6), implying that it is associated with fluctuations of the contacts driven by a potential drop that occurs mostly at the contacts, as previously proposed (15) and discussed in more detail below.…”

“…S3) above 0.1 V. It is a ubiquitous signal of protein capture, showing the same two-level switching in all cases. We originally observed these fluctuations for a protein captured in a fixed-junction chip (15) and although the present work uses an STM, we have replicated measurements of TN for one of the proteins studied here (anti-DNP) in a chip as well as in the STM to show that these are not some artifact of the measurement method. Examples of this TN are given in SI Appendix , Fig.…”

“…Reproducible two-point measurements of the conductance of molecules require reproducible contacts (14), so the reproducible observation of large (nS-scale) conductance fluctuations in single integrin molecules (bound to just one of two electrodes by their cognate ligands) was a surprising finding (15). This prior work did not probe the low bias region (where fluctuations were absent) owing to leakage currents that obscured any dc current through the protein.…”

The Vegetative Receptor-Vascular Reflex (VRVR) – A New Key to Regeneration

“…In view of the fact that important physiological processes utilize either quantum processes, for instance the photosynthetic effect in plants (Collini et al, 2010), or can be analyzed holistically similar to quantum processes (Turvey, 2015), and that proteins exhibit properties that are in a meta-stable critical quantum state (Vattay et al, 2015) it would not really be surprising to find that both the properties of single collagen molecules and the behavior of the connective tissue as a whole supports even more coherent processes than just piezoelectric ones. Indeed, it could recently be shown that certain proteins can become semiconductors and carry large electric charges, likely by a quantum process (Lindsay et al, 2017). And hemoglobin is different from chlorophyll, the molecule supporting photosynthesis, only by the fact that it contains a core of iron instead of magnesia.…”