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The Spectrum of Fluctuations in Living Matter

Project description

The fluctuating dynamics of living matter

Living matter is driven by energy-consuming microscopic processes like the action of molecular motors and cell division. These processes create active, non-equilibrium fluctuations that impact biological processes. However, unlike for thermal fluctuations, there is no theoretical framework for predicting active fluctuations. The ERC-funded LIVING_FLUCTUATIONS project aims to bridge this gap through theoretical research and experimental collaborations. First, at the subcellular scale, it aims to predict the active noise spectrum from the non-equilibrium binding kinetics of cytoskeletal proteins. Second, at the tissue scale, it aims to predict the statistical properties of pressure fluctuations due to stochastic cell proliferation. Ultimately, the project seeks to develop the stochastic hydrodynamics of living materials, shedding light on how active fluctuations drive biological functions in cells and tissues.

Objective

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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2023-STG

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Host institution

UNIVERSITAT DE BARCELONA
Net EU contribution
€ 1 339 631,74
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 Barcelona
Spain
Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 339 631,74

Beneficiaries (2)