Protons at the speed of sound: Predicting specific biological signaling from physics

Abstract

Local changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. membranes) would therefore constitute an important pillar towards a physical mechanism of biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physicochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification and propagate – in analogy to sound – at velocities controlled by the interface’s compressibility. With transient local pH changes of 0.6 directly observed at the interface and velocities up to 1.4 m/s this represents hitherto the fastest protonic communication observed. Furthermore simultaneously propagating mechanical and electrical changes in the lipid interface are detected, exposing the thermodynamic nature of these pulses. Finally, these pulses are excitable only beyond a threshold for protonation, determined by the pKa of the lipid head groups. This protonation-transition plus the existence of an enzymatic pH-optimum offer a physical basis for intra- and intercellular signaling via sound waves at interfaces, where not molecular structure and mechano-enyzmatic couplings, but interface thermodynamics and thermodynamic transitions are the origin of the observations.

It sounds like an action potential: unification of electrical, chemical and mechanical aspects of acoustic pulses in lipids

“…These include time and velocity scales, the appearance in multiple observables, an adiabatic temperature signal, a sigmoidal response to excitation, and annihilation upon collision. In addition, it was previously demonstrated that the membrane potential and the pH are locally affected by acoustic pulses in lipids [15,29]. In this work, we have continued this line of research, and demonstrated that electrical and pH aspects of acoustic pulses emerge from an idealized physical description of the lipid interface.…”

“…On the other hand, substances that adsorb on the acidic polar head; for example, protons, reduce the electric repulsion between the lipid molecules [14]. Thus, chemical changes at the lipid interface also accompany acoustic pulses [15,16]. An understanding of these electro-chemical effects appears crucial to the development of a realistic theory of acoustics in lipid interfaces.…”

On the Physical Basis of Biological Signaling by Interface Pulses

“…As demonstrated earlier 13,19 , the pulses that we describe are acoustic, and should not be confused with the chemical waves in excitable materials that were reported earlier [31][32][33] , in which chemical diffusion serves as the underlying mechanism for propagation. Here, no material 8 transport is necessary for propagation and communication of a signal (Footnote: Since this initiates exploration of a new concept in biology, we use the word 'communication' in its broadest sense as "production of an effect at a distance by a localized event").…”

Collision of two action potentials in a single excitable cell

“…Recently, evidence in favor of this proposition has been obtained. In lipid monolayers, linear [16,17] as well as nonlinear waves [18] have been excited and detected by a variety of means (e.g. chemically, mechanically, electrically, etc.).…”