Modulation of Lysenin’s Memory by Cu²⁺ Ions

Lysenin is a pore-forming protein extracted from the red earthworm E. fetida , which forms voltage-gated channels in artificial and natural lipid membranes. A prominent feature of the channels is their memory, originating in the conductance hysteresis that occurs during the application of slow oscillatory voltages. In this work, we showed this innate memory was strongly influenced by the addition of small amounts of Cu ²⁺ ions. After Cu ²⁺ addition, the lysenin channels previously closed by an applied voltage showed a stronger preference for the closed state, indicative of major changes in kinetics and equilibrium. However, the physiology behind this shift is still obscure. To fill this gap in our knowledge, we employed electrophysiology measurements to identify the changes in the closing and opening rates of lysenin channels exposed to Cu ²⁺ ions and step voltages. We found Cu ²⁺ simultaneously reduced the closing rates and increased the reopening rates, leading to a more prominent hysteretic behavior and improved memory. These findings may constitute the starting point on investigations of the memory of brainless microorganisms, and potential applications to bioelectronics and development of smart biological switches and nano-valves.