Physics-based modeling of whole-cell function: colloidal fundamentals to life-essential processes

A grand challenge of systems biology is an understanding of cells so complete that all cellular behavior can be determined from the composition and dynamics of constituent biomolecules. But connecting single-molecule to cellular behavior requires bridging processes that operate over nanoseconds and nanometers to those spanning minutes and microns. Yet the physical details of this intermediate realm are largely abstracted away in whole-cell kinetics models. Colloidal-scale physics bridges this gap and can reveal the relationship between physics and biological function. We demonstrate this by proposing that colloidal mechanisms regulate mRNA translation in E. Coli. We built a novel bio-colloidal modeling framework with nanometer resolution that explicitly and represents the transport and reaction dynamics of individual biomolecules as they interact and react over whole-cell-function time scales. We showed that Brownian motion is essential but insufficient to recover experimentally measured elongation rates; we proposed other colloidal physics mechanisms that close the gap. This is a general framework for discovering how colloid physics predict biological behavior.