Cellular Biophysics - Function


  Dr. Shiladitya BanerjeeDr. Srividya Iyer-Biswas, Tom KuntzCharlie Wright

How does a cell tell time? Is the noise of cellular processes related to temperature and to energy consumption? Can we describe cell functions with a "top down" statistical mechanics? How nonequilibrium are cellular processes? Can the cell cycle be controlled by extrinsic pulsatile chemical "forces?" [133] These are among the questions that are being addressed through single cell (optical microscopy) experiments of the bacterium Caulobacter crescentus. We are studying the cell cycle, primarily from a top-down perspective by measuring the time required for the cell cycle to occur (division time), the growth of the cell and fluorescent fusion-protein reporters of the expression levels of specific proteins. We have developed an integrated optical microscopy and automated image analysis approach that allows measuring a thousand single cells for ~100 generations (so 105 single cell growth curves) in a week-long experiment with a given set of environmental parameters. The enormous amounts of data generated allow addressing each biological question with statistically large data sets. The large generation number studies are made possible by a unique combination of molecular biology and microfluidics—therefore, we can study the same single cells for >100 generations and address fundamental questions about cell immortality and aging (senescence) with unprecedented insight. Stochastic simulations of network models are used to interpret the high level data. Our theoretical insights come from phenomenological descriptions of the observables through Langevin, Master and Fokker-Planck equation formalism. Amazingly, this biological system shows scaling behavior in its temperature-dependent dynamics, chemically controllable aging, and synchronization to external "clock-like" perturbations. We are currently investigating the applicability of linear response and whether the cell cycle obeys a fluctuation-dissipation relationship. Since we can control the state of the cell and drive it to new states, the bacterium allows addressing current frontier questions in the statistical mechanics of nonequlibrium steady-states and their dynamics.

Single-cell visualization of a thin film of aquatic bacterial cells (C. crescentus) developing inside a microfluidic chamber.