Periodic Reporting for period 2 - MolecularControl (Harvesting out-of-equilibrium forces for molecular control)
Okres sprawozdawczy: 2022-06-01 do 2023-05-31
Numerous biological processes harvest out-of-equilibrium forces for transport, sensing, signaling and more. For example, pumping of ions is performed within fluctuating pores that are believed to facilitate transport. The nature of these forces is extremely diverse, from electrical driving to thermodynamic or chemical driving. The ability to describe nonequilibrium states is critical to understand numerous biological processes but is extremely challenging as standard thermodynamic concepts fail. The MolecularControl project has investigated transport properties in out-of-equilibrium systems relevant to health issues or sustainable energy. It has developed theoretical tools that can be widely applied, and transferred to other soft matter problems.
MolecularControl has addressed several soft matter contexts and probed the mechanisms for particle transport at small scales in diverse environments. These include transport in nanopores or nanochannels (Part 1) as well as the transport of complex small particles with multivalent ligand-receptors (Part 2).
Part 1 - Transport in nanopores
Fluctuations are ubiquitous in bio and artificial nanopores, and dramatically impact transport since the surface-to-volume ratio is exacerbated in small pores. Most of the time, fluctuations are seen as a negative feature that impedes for example signal measurements. Furthermore, fluctuations have entangled consequences, as they affect all dynamics and dynamics are not necessarily linear. Yet, biological pores (such as ion channels that serve as chemical pathways between cells) are still able to achieve complex tasks, including precise and rapid selection of particles, in spite of fluctuations.
To investigate the riddle of fluctuations in nanopore transport, we explored how fluctuations in the number of particles present within the pore affect signal measurements, and have published several original research articles on the subject.
Beyond number fluctuations, transport of ions and particles in small pores is strongly affected by hydrodynamic and electrokinetic effects, as we have further demonstrated.
Collaborating with researchers in Europe and at NYU, a methodological review was written to disseminate and communicate about modern tools and methods to account for such effects in small pores.
Part 2 - Transport of particles with sticky feet or multivalent ligand-receptors.
Particles with sticky feet - or nanoscale caterpillars - in biological or artificial systems, beat the paradigm of standard diffusion to achieve complex functions. Some cells (like leucocytes) use ligand-receptor contacts (sticky feet) to crawl and roll along vessels. Numerous viruses utilize proteins to stick and roll and crawl on mucus proteins before invading their host. Sticky DNA (another type of sticky feet) is coated on colloids to design programmable interactions and self-assembly.
We have rationalized what parameters control average feet attachment in a model system and how they can be compared to other existing systems, using modeling approaches and experiments.
We have investigated furthermore how various motion modes of such particles (sliding or hopping) may be favored over one another, especially depending on the number of feet attached. This was done building an advanced yet completely analytically solvable modeling approach, that showed predictive capabilities. After a series of experiments we were able to demonstrate these different motion modes on a model experimental system and showed how they depend on several parameters such as temperature.
Finally we have identified that such particles may diffuse with a diffusion coefficient that depends on their mass: this breaks the common physical paradigm where inertial effects do not arise in the diffusion of small scale systems.
All results have been published as green or gold open access publications, as well as open access codes; and have been broadly disseminated at multiple scales, in conferences, seminars, meetings and social media.
Part 1 - Transport in nanopores
Fluctuations are ubiquitous in bio and artificial nanopores, and dramatically impact transport since the surface-to-volume ratio is exacerbated in small pores. Most of the time, fluctuations are seen as a negative feature that impedes for example signal measurements. Furthermore, fluctuations have entangled consequences, as they affect all dynamics and dynamics are not necessarily linear. Yet, biological pores (such as ion channels that serve as chemical pathways between cells) are still able to achieve complex tasks, including precise and rapid selection of particles, in spite of fluctuations.
To investigate the riddle of fluctuations in nanopore transport, we explored how fluctuations in the number of particles present within the pore affect signal measurements, and have published several original research articles on the subject.
Beyond number fluctuations, transport of ions and particles in small pores is strongly affected by hydrodynamic and electrokinetic effects, as we have further demonstrated.
Collaborating with researchers in Europe and at NYU, a methodological review was written to disseminate and communicate about modern tools and methods to account for such effects in small pores.
Part 2 - Transport of particles with sticky feet or multivalent ligand-receptors.
Particles with sticky feet - or nanoscale caterpillars - in biological or artificial systems, beat the paradigm of standard diffusion to achieve complex functions. Some cells (like leucocytes) use ligand-receptor contacts (sticky feet) to crawl and roll along vessels. Numerous viruses utilize proteins to stick and roll and crawl on mucus proteins before invading their host. Sticky DNA (another type of sticky feet) is coated on colloids to design programmable interactions and self-assembly.
We have rationalized what parameters control average feet attachment in a model system and how they can be compared to other existing systems, using modeling approaches and experiments.
We have investigated furthermore how various motion modes of such particles (sliding or hopping) may be favored over one another, especially depending on the number of feet attached. This was done building an advanced yet completely analytically solvable modeling approach, that showed predictive capabilities. After a series of experiments we were able to demonstrate these different motion modes on a model experimental system and showed how they depend on several parameters such as temperature.
Finally we have identified that such particles may diffuse with a diffusion coefficient that depends on their mass: this breaks the common physical paradigm where inertial effects do not arise in the diffusion of small scale systems.
All results have been published as green or gold open access publications, as well as open access codes; and have been broadly disseminated at multiple scales, in conferences, seminars, meetings and social media.
Mixing particles is an everyday experience, like stirring your morning coffee with a spoon. At the nanoscale -- for example for small biological organisms -- such tools do not exist, making mixing and transport in general a challenge. Here we have found alternative strategies to mix, transport and achieve complex functions at such small scales. For that we have developped a number of advanced mathematical and numerical tools to model and predict the behavior of specific small scale systems.
We have also helped to establish and understand well-controlled experiments that mimic those systems. Ultimately this could provide design principles for new technologies in the biomedical and energy fields. Concretely, in the different applications reached by the MolecularControl project, this is what we can expect:
Part 1 - Transport in nanopores
Understanding the traces left by fluctuations in nanopores is a challenging task due to the variety of processes at play. Yet, investigating number fluctuations in model nanopores allowed us to provide guidelines for the characteristic sizes that favor or modify fluctuations. These guidelines could open new avenues in artificial designs, to harness fluctuations for improved filtration and sensing devices.
Part 2 - Transport of particles with sticky feet or multivalent ligand-receptors.
Predicting the dynamics of such sticky motion is challenging since sticky events (attaching/detaching) often occur on very short time scales compared to the overall motion of the particle. Even understanding the equilibrium statistics of these systems (how many feet are attached in average) is largely uncharted. Yet, controlling the dynamics of such particles is critical to achieve advanced functions: for example facilitating rolling is critical for long-range alignment of DNA coated-colloids crystals, and predicting how the chemical interactions of the feet modify displacement is key to predict and potentially inhibit virus infection. We have put together a formula that allows one to predict how fast and how such a particle will move.
We have also helped to establish and understand well-controlled experiments that mimic those systems. Ultimately this could provide design principles for new technologies in the biomedical and energy fields. Concretely, in the different applications reached by the MolecularControl project, this is what we can expect:
Part 1 - Transport in nanopores
Understanding the traces left by fluctuations in nanopores is a challenging task due to the variety of processes at play. Yet, investigating number fluctuations in model nanopores allowed us to provide guidelines for the characteristic sizes that favor or modify fluctuations. These guidelines could open new avenues in artificial designs, to harness fluctuations for improved filtration and sensing devices.
Part 2 - Transport of particles with sticky feet or multivalent ligand-receptors.
Predicting the dynamics of such sticky motion is challenging since sticky events (attaching/detaching) often occur on very short time scales compared to the overall motion of the particle. Even understanding the equilibrium statistics of these systems (how many feet are attached in average) is largely uncharted. Yet, controlling the dynamics of such particles is critical to achieve advanced functions: for example facilitating rolling is critical for long-range alignment of DNA coated-colloids crystals, and predicting how the chemical interactions of the feet modify displacement is key to predict and potentially inhibit virus infection. We have put together a formula that allows one to predict how fast and how such a particle will move.