LIVING_FLUCTUATIONS · The Spectrum of Fluctuations in Living Matter

Living matter is active: It is driven far from thermodynamic equilibrium by irreversible microscopic processes, such as the action of molecular motors and cell division. This microscopic activity generates nonequilibrium fluctuations, which overwhelm thermal noise and impact biological processes across scales, from intracellular transport to tumour formation. However, unlike in the case of thermal fluctuations, we have no theoretical framework like the fluctuation-dissipation theorem to predict the statistical properties of active fluctuations. Here, I propose to address this knowledge gap by means of theoretical research combined with experimental collaborations organized in two aims.In the first aim, at the subcellular scale, we will predict the spectrum of active noise based on the nonequilibrium binding kinetics of cytoskeletal proteins. To this end, we will coarse-grain a cytoskeletal network model in which detailed balance is explicitly broken at the molecular scale. We will then use the predictions to analyse experimental data and infer features of molecular activity in living cells and in the mitotic spindle.In the second aim, at the tissue scale, we will predict the statistical properties of active pressure fluctuations due to stochastic cell proliferation, which is itself regulated by pressure. We will establish how this mechanical feedback affects the spectrum of the pressure field in a growing tissue. To this end, we will generalize tools from the renormalization group that were originally developed to study nonequilibrium critical phenomena through the Kardar-Parisi-Zhang equation. We will then collaborate with experimentalists to test our predictions by measuring the spectrum of pressure fluctuations in living tissues for the first time.Overall, this research will lay the basis of a stochastic hydrodynamics of living materials and, at the same time, reveal how active fluctuations promote biological functions in cells and tissues.