Simulating biological processes: Stochastic physics from whole cells to colonies

Tyler M. Earnest, John A. Cole, Zaida Luthey-Schulten

Research output: Contribution to journalReview article

Abstract

The last few decades have revealed the living cell to be a crowded spatially heterogeneous space teeming with biomolecules whose concentrations and activities are governed by intrinsically random forces. It is from this randomness, however, that a vast array of precisely timed and intricately coordinated biological functions emerge that give rise to the complex forms and behaviors we see in the biosphere around us. This seemingly paradoxical nature of life has drawn the interest of an increasing number of physicists, and recent years have seen stochastic modeling grow into a major subdiscipline within biological physics. Here we review some of the major advances that have shaped our understanding of stochasticity in biology. We begin with some historical context, outlining a string of important experimental results that motivated the development of stochastic modeling. We then embark upon a fairly rigorous treatment of the simulation methods that are currently available for the treatment of stochastic biological models, with an eye toward comparing and contrasting their realms of applicability, and the care that must be taken when parameterizing them. Following that, we describe how stochasticity impacts several key biological functions, including transcription, translation, ribosome biogenesis, chromosome replication, and metabolism, before considering how the functions may be coupled into a comprehensive model of a 'minimal cell'. Finally, we close with our expectation for the future of the field, focusing on how mesoscopic stochastic methods may be augmented with atomic-scale molecular modeling approaches in order to understand life across a range of length and time scales.

Original languageEnglish (US)
Article number052601
JournalReports on Progress in Physics
Volume81
Issue number5
DOIs
StatePublished - Apr 5 2018

Keywords

  • chemical master equation
  • flux balance analysis
  • gene expression
  • metabolism
  • reaction-diffusion master equation
  • stochastic chemical kinetics
  • whole-cell modeling

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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