Cellular metabolism and colloids: Realistically linking physiology and biological physical chemistry

Important concepts from colloidal physical chemistry such as coacervation, phase transitions, emergent properties and ionic association, are currently emerging in the lexicon of cellular biology, prompted mostly by recent experimental observations of liquid phase coexistence in the cell cytosol. Nevertheless, from an historical point of view, the application of these concepts in cell biology is not new. They were key concepts into the so-called protoplasmic doctrine, an alternative (and largely forgotten) approach to cell physiology. The most complete theory originating from this line of thinking was the Association-Induction Hypothesis (AIH), introduced by Gilbert N. Ling in 1962. The AIH, which envisions living cells as complex dynamical colloidal systems, provides ample theory and experimental evidence to call into question the now dominant view of living cells as fluid-filled vesicles. This review attempts to present and discuss the usefulness of the AIH to understand a series of experimental observations from our laboratory from living suspensions of the yeast Saccharomyces cerevisiae exhibiting glycolytic oscillations. Particularly, the AIH helped us integrate, in a mechanistic sense, the basis of a strong temporal coupling observed between ATP and a series of cellular properties such as intracellular water dipolar relaxation, intracellular K⁺ concentration, among many others, where the colloidal physical chemistry of the cell interior plays a fundamental role.