Murburn concept in cellular function and bioenergetics, Part 2: Understanding integrations-translations from molecular to macroscopic levels

Thermogenesis, electro-chemical physiology (ECP), and electro-mechanical activities (EMAs) are fundamental facets of cellular functioning that are associated with powering, coherence, homeostasis, sensing, and response to stimuli. The classical Hodgkin–Huxley–Katz purview of ECP is derived from Nernst-based foundations for dilute solutions, whereas cellular milieus are mostly highly packed colloidal coacervates, with various types/levels of macromolecules (ions), interactions, and ordering of water. It has also been established that trans-membrane potential (TMP) manifestation can also be affected by adsorption of ions and effective charge separation (1e processes), necessitating the questioning and expansion of classical purviews. Further, we have demonstrated that the traditional explanation of electrogenic/stoichiometric and vitally deterministic bidirectional pumping/channeling of ions by membrane proteins (such as Na,K-ATPase) as the rationale for resting/dynamic TMP variations is untenable. In stark contrast, the murburn purview of ECP-EMAs acknowledges the complexity and discretization of the organization of water, ions, and macromolecules within the cell and does not solicit selective ion-pumping or TMP-based powering/propagation rationales. Herein, we summarize the murburn rationale for the molecular to macroscopic integration of processes such as thermogenesis, kinetic Na–K differentiation at the cell membrane, visual signal transduction and neuronal impulse relay, Complex V mediated mechano-chemostat function, flagella-based motility, etc., and discuss the alteration of cellular volume/tenor in muscle cell contraction. We assert that the membrane-embedded proteins/enzymes cannot use ATP to work against the natural laws of physics. Therefore, the classical perception of membrane-based ion pumps must be jettisoned to make way for the thermodynamics-friendly murburn purview.