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Heatomics for life

Obiettivo

Living cells are the paradigm of energy and information processing machines. To remain alive, they avoid thermodynamic equilibrium by adopting and maintaining a stable nonequilibrium steady state (NESS). To achieve this, cells draw on external energy sources through a myriad of molecular reactions that continuously dissipate energy to the environment as heat. The heat dissipated per unit time, known as the entropy production rate σ, is the hallmark of nonequilibrium physics and of NESS itself. We posit that σ is life’s universal and most essential signature and a unique descriptor of cellular state. Its measurement provides a direct window into understanding how life works. Despite many efforts, measurements of this fundamental quantity at the nanoscale remain challenging. Recently, we have introduced a method called the variance sum rule (VSR), based on flickering signals of position and force, that enables the determination of σ in NESS systems.

Using a radically new conceptual and experimental framework, we will measure σ at the level of single catalytic reactions, single molecular motors, and individual cells -down to subcellular organelles- by combining mechanical and fluorescence measurements. We will focus on three interlaced objectives: (1) measure σ in catalytic reactions using mechanical probes, from oxidoreductases to hydrolases; (2) determine σ in single redox reactors, molecular motors, and in information-to-energy transduction in DNA and RNA polymerases; and (3) measure the σ-map in single cells, such as the thermoregulating brown adipocytes and the extracellularly active fibroblasts. Our multiscale approach will integrate mechanical measurements with optical tweezers and fluorescence lifetime imaging microscopy (FLIM) of living cells, together with theoretical modeling of nonequilibrium systems. This work will yield new fundamental insights into the physical principles governing cellular function and the role of heat in living matter.

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Istituzione ospitante

UNIVERSITAT DE BARCELONA
Contributo netto dell'UE
€ 2 467 625,00
Indirizzo
GRAN VIA DE LES CORTS CATALANES 585
08007 Barcelona
Spagna
Regione
Este Cataluña Barcelona
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)