Temporal metabolic partitioning of the yeast and protist cellular networks: the cell is a global scale-invariant (fractal or self-similar) multioscillator

Britton Chance, electronics expert when a teenager, became an enthusiastic student of biological oscillations, passing on this enthusiasm to many students and colleagues, including one of us (DL). This historical essay traces BC’s influence through the accumulated work of DL to DL’s many collaborators. The overall temporal organization of mass-energy, information, and signaling networks in yeast in self-synchronized continuous cultures represents, until now, the most characterized example of in vivo elucidation of time structure. Continuous online monitoring of dissolved gases by direct measurement (membrane-inlet mass spectrometry, together with NAD(P)H and flavin fluorescence) gives strain-specific dynamic information from timescales of minutes to hours as does two-photon imaging. The predominantly oscillatory behavior of network components becomes evident, with spontaneously synchronized cellular respiration cycles between discrete periods of increased oxygen consumption (oxidative phase) and decreased oxygen consumption (reductive phase). This temperature-compensated ultradian clock provides coordination, linking temporally partitioned functions by direct feedback loops between the energetic and redox state of the cell and its growing ultrastructure. Multioscillatory outputs in dissolved gases with 13 h, 40 min, and 4 min periods gave statistical self-similarity in power spectral and relative dispersional analyses: i.e., complex nonlinear (chaotic) behavior and a functional scale-free (fractal) network operating simultaneously over several timescales.