Scaling laws governing stochastic growth and division of single bacterial cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-11, Vol.111 (45), p.15912-15917
• Main Authors: Iyer-Biswas, Srividya, Wright, Charles S., Henry, Jonathan T., Lo, Klevin, Burov, Stanislav, Lin, Yihan, Crooks, Gavin E., Crosson, Sean, Dinner, Aaron R., Scherer, Norbert F.
• Format: Article
• Language: English
• Subjects: Analysis; Bacteria; Biological Sciences; Caulobacter crescentus - growth & development; Cell cycle; Cell Division - physiology; Cell growth; Cells; Daughter cells; Experiments; Fall lines; Geometric growth; Models, Biological; Physical Sciences; Population growth; Power laws; Stochastic models; Stochastic Processes; Temperature; Temperature distribution
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1403232111

Uncovering the quantitative laws that govern the growth and division of single cells remains a major challenge. Using a unique combination of technologies that yields unprecedented statistical precision, we find that the sizes of individual Caulobacter crescentus cells increase exponentially in time. We also establish that they divide upon reaching a critical multiple (≈1.8) of their initial sizes, rather than an absolute size. We show that when the temperature is varied, the growth and division timescales scale proportionally with each other over the physiological temperature range. Strikingly, the cell-size and division-time distributions can both be rescaled by their mean values such that the condition-specific distributions collapse to universal curves. We account for these observations with a minimal stochastic model that is based on an autocatalytic cycle. It predicts the scalings, as well as specific functional forms for the universal curves. Our experimental and theoretical analysis reveals a simple physical principle governing these complex biological processes: a single temperature-dependent scale of cellular time governs the stochastic dynamics of growth and division in balanced growth conditions. Significance Growth and division of individual cells are the fundamental events underlying many biological processes, including the development of organisms, the growth of tumors, and pathogen–host interactions. Quantitative studies of bacteria can provide insights into single-cell growth and division but are challenging owing to the intrinsic noise in these processes. Now, by using a unique combination of measurement and analysis technologies, together with mathematical modeling, we discover quantitative features that are conserved across physiological conditions. These universal behaviors reflect the physical principle that a single timescale governs noisy bacterial growth and division despite the complexity of underlying molecular mechanisms.