Cell size and cell cycle control

Microbes such as bacteria and yeast are able to maintain a narrow distribution of cell sizes by regulating the timing of cell divisions. In rich nutrient conditions, bacteria such as E. coli divide faster than their chromosomes replicate (!), implying that cells maintain multiple ongoing rounds of chromosome replication. How these processes are coupled and controlled is a fundamental question in cellular biology. We have shown that ideas from statistical physics are helpful in deciphering this problem, and in particular lead to insights into the structure of the correlations between cell cycle parameters.  The models also account for the tight coupling between size control and DNA replication. Results on budding yeast and archaea show similar behavior, suggesting that the principles involved may be prevalent in Nature across different domains of life - for reasons yet to be elucidated.

Relevant publications:

  • Ariel Amir, Cell size regulation in bacteria, Physical Review Letters 112, 208102 (2014), highlighted in Physics 7, 55 (2014).
  • Andrew Marantan and Ariel Amir, Stochastic modeling of cell growth with symmetric or asymmetric division, Physical Review E 94, 012405 (2016).
  • Felix Barber, Po-Yi Ho, Andrew Murray and Ariel Amir, Details matter: noise and model structure set the relationship between cell size and cell cycle timing, Frontiers in Cell and Developmental Biology (special issue on "Determinants of Cell Size") 5, 92 (2017).
  • Po-Yi Ho, Jie Lin and Ariel Amir, Modeling cell size regulation: From single-cell level statistics to molecular mechanisms and population level effects, Annual Review of Biophysics 47, 251 (2018), invited review.
  • Ariel Amir and Nathalie Q. Balaban, Learning from noise: how observing stochasticity may aid microbiology, Trends in Microbiology (special issue on "Broad concepts in microbiology") 26, 374 (2018), invited review.
  • Ilya Soifer, Lydia Robert and Ariel Amir, Single-cell analysis of growth in budding yeast and bacteria reveals a common size regulation strategy, Current Biology 26, 356 (2016).
  • Ye-Jin Eun, Po-Yi Ho, Minjeong Kim, Lars Renner, Salvatore LaRussa, Lydia Robert, Amy Schmid, Ethan Garner and Ariel Amir, Archaeal cells share common size control with bacteria despite noisier growth and division, Nature Microbiology 3, 148 (2018), cover article.
  • Felix Barber, Ariel Amir and Andrew W. Murray, Cell-size regulation in budding yeast does not depend on linear accumulation of Whi5, Proceedings of the National Academy of Sciences 117, 14243 (2020).
  • Po-Yi Ho and Ariel Amir, Simultaneous Regulation of Cell Size and Chromosome Replication in Bacteria, Frontiers in Microbiology (special issue on "The Bacterial Cell: Coupling between Growth, Nucleoid Replication, Cell Division and Shape") 6, 662 (2015), invited article.
  • Hai Zheng, Po-Yi Ho, Meiling Jiang, Bin Tang, Weirong Liu, Dengjin Li, Xuefeng Yu, Nancy E. Kleckner, Ariel Amir and Chenli Liu, Interrogating the Escherichia coli cell cycle by cell dimension perturbations, Proceedings of the National Academy of Sciences 113, 15000 (2016).
  • Ariel Amir, Is cell size a spandrel?, eLife 6, e22186 (2017).
  • Michelle M. Logsdon, Po-Yi Ho, Kadamba Papavinasasundaram, Kirill Richardson, Christopher M. Sassetti, Ariel Amir and Bree B. Aldridge, A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization, Current Biology 27, 3367–3374 (2017).
  • Po-Yi Ho, Bruno M.C. Martins and Ariel Amir, A mechanistic model of the regulation of division timing by the circadian clock in cyanobacteria, Biophysical Journal 118, 2905 (2020).
  • P. Kar, S. Tiruvadi-Krishnan, J. Männik, J. Männik and A. Amir, Distinguishing different modes of growth using single-cell data, eLife 10, e72565 (2021).
  • S. Tiruvadi-Krishnan, J. Männik, P. Kar, J. Lin, A. Amir and J. Männik, Coupling between DNA replication, segregation, and the onset of constriction in Escherichia coli, Cell Reports 38, 110539 (2022).
  • P. Kar, S. Tiruvadi-Krishnan, J. Männik, J. Männik and A. Amir, Using conditional independence tests to elucidate causal links in cell cycle regulation in Escherichia coli, Proceedings of the National Academy of Sciences 120, e2214796120 (2023).
  • J. Männik, P. Kar, C. Amarasinghe, A. Amir and J. Männik, Determining the rate-limiting processes for cell division in Escherichia coli, Nature Communications 15, 9948 (2024).
  • E.S. Chung, P. Kar, M. Kamkaew, A. Amir and B.B. Aldridge, Single-cell imaging of the Mycobacterium tuberculosis cell cycle reveals linear and heterogeneous growth, Nature Microbiology 9, 3332–3344 (2024).
  • P. Kar and A. Amir, Are cell length and volume interchangeable in cell cycle analysis?, Biophysical Journal 124, 1424–1432 (2025), cover article.