Scanning probe methods have been used to measure the effect of electrochemical potentialand applied force on the tunnelling conductance of the redox metalloprotein yeastiso-1-cytochrome c (YCC) at a molecular level. The interaction of a proximal probe withany sample under test will, at this scale, be inherently perturbative. This is demonstratedwith conductive probe atomic force microscopy (CP-AFM) current–voltage spectroscopy inwhich YCC, chemically adsorbed onto pristine Au(111) via its surface cysteine residue, isobserved to become increasingly compressed as applied load is increased, with concomitantdecrease in junction resistance. Electrical contact at minimal perturbation, whereprobe–molecule coupling is comparable to that in scanning tunnelling microscopy, bringswith it the observation of negative differential resistance, assigned to redox-assistedprobe–substrate tunnelling. The role of the redox centre in conductance is alsoresolved in electrochemical scanning tunnelling microscopy assays where molecularconductance is electrochemically gateable through more than an order of magnitude.