Fabrizio Cleri

A stochastic grain growth model based on a variational principle for dissipative systems

A stochastic model for the evolution of a cellular network driven by dissipative forces is presented. The model is based on a variational formulation for the dissipated power, from which we obtain an expression for the transition-rate generating function to be used in kinetic Monte Carlo simulations. The model canonical variables are the positions and velocities of the network vertices where cell walls meet. We apply such a model to the study of grain growth in two dimensions, in which the network represents a cross-section of a polycrystalline microstructure and the cell walls represent grain boundaries. The results of the stochastic grain-growth model for relevant statistical quantities are compared to deterministic model results and analytic theories.

Stochastic mechanical degradation of multi-cracked fiber bundles with elastic and viscous interactions

The mechanics of fiber bundles has been largely investigated in order to understand their complex failure modes. Under a mechanical load, the fibers fail progressively while the load is redistributed among the unbroken fibers. The classical fiber bundle model captures the most important features of this rupture process. On the other hand, the homogenization techniques are able to evaluate the stiffness degradation of bulk solids with a given population of cracks. However, these approaches are inadequate to determine the effective response of a degraded bundle where breaks are induced by non-mechanical actions. Here, we propose a method to analyze the behavior of a fiber bundle, undergoing a random distribution of breaks, by considering the intrinsic response of the fibers and the visco-elastic interactions among them. We obtain analytical solutions for simple configurations, while the most general cases are studied by Monte Carlo simulations. We find that the degradation of the effective bundle stiffness can be described by two scaling regimes: a first exponential regime for a low density of breaks, followed by a power-law regime at increasingly higher break density. For both regimes, we find analytical effective expressions described by specific scaling exponents.Graphical abstract

Monte Carlo simulations of single polymer force-extension relations

We present Monte Carlo simulations for studying the statistical mechanics of arbitrarily long single molecules under stretching. In many cases in which the thermodynamic limit is not satisfied, different statistical ensembles yield different macroscopic force-displacement curves. In this work we provide a description of the Monte Carlo simulations and discuss in details the assumptions adopted.

Tunneling mechanism and contact mechanics of colloidal nanoparticle assemblies

Nanoparticle assemblies with thiol-terminated alkyl chains are studied by conducting atomic force microscopy (c-AFM) regarding their use as strain gauges for touch-sensitive panels. Current-force spectroscopy is used as a characterization tool complementary to the macroscopic setup since it allows a bias to be applied to a limited number of junctions, overcoming the Coulomb blockade energy and focusing on the contact electromechanics and the transport mechanism across the ligand. First, transition voltage spectroscopy is applied with varying force to target the underlying tunneling mechanism by observing whether the transition between the ohmic and exponential current-voltage behavior is force-dependent. Secondly, current-force spectroscopy in the ohmic range below the transition voltage is performed. The current-force behavior of the AFM probe in contact with a nanoparticle multilayer is associated with the spread of force and current within the nanoparticle lattice and at the level of adjacent particles by detailed contact mechanics treatment. The result is twofold: concerning the architecture of sensors, this work is a sample case of contact electromechanics at scales ranging from the device scale down to the individual ligand molecule. Regarding transport across the molecule, the vacuum tunneling mechanism is favored over the conduction by coherent molecular states, which is a decision-making aid for the choice of ligand in applications.

A biophysical model of cell evolution after cytotoxic treatments: Damage, repair and cell response

We present a theoretical agent-based model of cell evolution under the action of cytotoxic treatments, such as radiotherapy or chemotherapy. The major features of cell cycle and proliferation, cell damage and repair, and chemical diffusion are included. Cell evolution is based on a discrete Markov chain, with cells stepping along a sequence of discrete internal states from normal to inactive. Probabilistic laws are introduced for each type of event a cell can undergo during its life: duplication, arrest, senescence, damage, reparation, or death. We adjust the model parameters on a series of cell irradiation experiments, carried out in a clinical LINAC, in which the damage and repair kinetics of single- and double-strand breaks are followed. Two showcase applications of the model are then presented. In the first one, we reconstruct the cell survival curves from a number of published low- and high-dose irradiation experiments. We reobtain a very good description of the data without assuming the well-known linear-quadratic model, but instead including a variable DSB repair probability. The repair capability of the model spontaneously saturates to an exponential decay at increasingly high doses. As a second test, we attempt to simulate the two extreme possibilities of the so-called bystander effect in radiotherapy: the local effect versus a global effect, respectively activated by the short-range or long-range diffusion of some factor, presumably secreted by the irradiated cells. Even with an oversimplified simulation, we could demonstrate a sizeable difference in the proliferation rate of non-irradiated cells, the proliferation acceleration being much larger for the global than the local effect, for relatively small fractions of irradiated cells in the colony.

Mechanical evolution of DNA double-strand breaks in the nucleosome

Double strand breaks (DSB) in the DNA backbone are the most lethal type of defect induced in the cell nucleus by chemical and radiation treatments of cancer. However, little is known about the outcomes of damage in nucleosomal DNA, and on its effects on damage repair. We performed microsecond-long molecular dynamics computer simulations of nucleosomes including a DSB at various sites, to characterize the early stages of the evolution of this DNA lesion. The damaged structures are studied by the essential dynamics of DNA and histones, and compared to the intact nucleosome, thus exposing key features of the interactions. All DSB configurations tend to remain compact, with only the terminal bases interacting with histone proteins. Umbrella sampling calculations show that broken DNA ends at the DSB must overcome a free-energy barrier to detach from the nucleosome core. Finally, by calculating the covariant mechanical stress, we demonstrate that the coupled bending and torsional stress can force the DSB free ends to open up straight, thus making it accessible to damage signalling proteins.