(64e) Colloidal Physics Instantiate Life in Biological Cells

We report a study of how physics at the colloidal scale instantiate life in biological cells. While principles from physics have driven recent paradigm shifts in how collective biomolecular behaviors orchestrate life, many mechanistic aspects of e.g. transcription, translation, and condensation remain mysterious because understanding and controlling them requires unifying two disparate physical regimes: the atomistic (structural biology) and the microscopic (systems biology). Colloidal-scale modeling bridges this divide and links molecular-scale behaviors to whole-cell function. I will discuss our computational model of a bacterial cell, Escherichia coli, where we represent biomolecules and their interactions physically and chemically, individually and explicitly. With it, we tackle a fundamental open question in biology, from a physico-chemical perspective: why protein synthesis speeds up during faster E. coli growth. We report a new mechanism, “stoichiometric crowding”, that leads to a previously undiscovered increase in ribosome productivity that in turn drives the speedup in protein synthesis. More generally, our computational study of protein synthesis in E. coli from the tandem perspective of cell biology and meso-scale physics presents a unique opportunity to broadly explore how the physical state of the cell impacts biological function. Our next steps are to use what we have learned to build a physics-based model of the minimal cell JCVI-syn3a.