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Nanoprobes for Nonequilibrium Driven Systems

Project description

Nanotechnology unveils the thermodynamics of microscopic activity

Live cells contain motor proteins that are responsible for key biological functions, including intracellular transport of cargo and cell division. Motor proteins convert chemical energy into mechanical motion, but little is known about the thermodynamics of these processes and the amount of energy lost to dissipation. The key objective of the EU-funded NanoNonEq project is to tackle conceptual challenges associated with the measurement of the stochastic dynamics of such biological processes. Researchers will develop fluorescent nanosensors that will allow them to detect the microscopic activity of motor proteins. These nanosensors will be functionalised for use in biomimetic models of biological systems and live cells to infer quantitative information on dissipation.

Objective

At the core of far-from-equilibrium biological activity lies an orchestra of molecular motors, constantly dissipating energy while converting chemical fuel into mechanical work. Estimating the amount of the free energy budget lost to dissipation is crucial for a deeper understanding of the underlying nonequilibrium dynamics and for unravelling the thermodynamic constraints on the possible biological processes. Although there are theoretical tools for quantifying nonequilibrium activity and dissipation in the framework of stochastic thermodynamics, there is a gap between these analytical calculations and their experimental applicability. The difficulty stems from the limited accessibility to the myriad degrees of freedom of complex systems and the finite measurement resolution, which can mask the footprints of nonequilibrium dynamics, such that they may appear as passive thermal fluctuations.
I will address this challenge both experimentally and theoretically. In my lab, I will develop fluorescent nanosensors for unveiling microscopic activity otherwise inaccessible in complex biological systems. Fluorescent single-walled carbon nanotubes with tailored functionalization will transduce molecular-motor activity to a modulation of the emitted fluorescence, providing a novel degree of freedom never before exploited as a phase-space coordinate for inferring dissipation in nonequilibrium systems. I will incorporate the nanotube sensors in minimal biomimetic models of active systems, including DNA-gel and reconstituted cytoskeleton driven by molecular motors, to demonstrate my approach in a highly controlled environment. Further, I will internalize the nanotubes within live cells, and utilize the fluorescence signal to estimate the dissipation in nonequilibrium intracellular organization. In parallel, I will advance theoretical tools for estimating the dissipation from experimental data, based on an approach I have pioneered for detecting time-irreversibility.

Host institution

TEL AVIV UNIVERSITY
Net EU contribution
€ 1 500 000,00
Total cost
€ 1 500 000,00

Beneficiaries (1)