Cell density dependence of oscillatory metabolism

Abstract

THERE is increasing evidence^1–3 that the behaviour of cell populations is determined not only by the behaviour of the individual cells, but also by their mutual interactions. One influence on the strength of these interactions may be cellular proximity which, in turn, is a function of cell density. For example, myoblasts fuse only when they reach a critical cell density⁴. The oscillatory glycolytic metabolism of the yeast Saccharomyces carlsbergensis has provided a convenient system for the exploration of several biochemical phenomena⁵. For example, whereas yeast cells are generally considered to be metabolically non-interacting, a coupling process of unknown character causes metabolic synchronisation of all cells to a common oscillatory frequency and phase⁶. A suspension of metabolically oscillating yeast therefore behaves as a population of strongly interacting units. Because continuous monitoring of amplitude and phase by fluorometry provides a constant assay of metabolic dynamics, any perturbation of these dynamics is easily recognised as a deviation from the predictable waveform. We describe here modifications in the metabolic behaviour of intact cell suspensions achieved by manipulating the strength of their interaction through changes in cell density.