Alessandro L. Sellerio

Overshoot during phenotypic switching of cancer cell populations.

The dynamics of tumor cell populations is hotly debated: do populations derive hierarchically from a subpopulation of cancer stem cells (CSCs), or are stochastic transitions that mutate differentiated cancer cells to CSCs important? Here we argue that regulation must also be important. We sort human melanoma cells using three distinct cancer stem cell (CSC) markers — CXCR6, CD271 and ABCG2 — and observe that the fraction of non-CSC-marked cells first overshoots to a higher level and then returns to the level of unsorted cells. This clearly indicates that the CSC population is homeostatically regulated. Combining experimental measurements with theoretical modeling and numerical simulations, we show that the population dynamics of cancer cells is associated with a complex miRNA network regulating the Wnt and PI3K pathways. Hence phenotypic switching is not stochastic, but is tightly regulated by the balance between positive and negative cells in the population. Reducing the fraction of CSCs below a threshold triggers massive phenotypic switching, suggesting that a therapeutic strategy based on CSC eradication is unlikely to succeed.

Deformation and failure of curved colloidal crystal shells

Significance Substantial experimental and theoretical work has been devoted to understand the equilibrium properties of curved crystals, but these crystals’ stability under mechanical forces remains largely unexplored and unknown. Understanding how curved crystals can adapt their shape and resist failure is of fundamental importance because these structures are at the forefront in the drive to fabricate new functionalized self-assembled materials. Here, we address these questions by numerical simulations of the deformation of colloidal crystalline shells. Our results highlight the fundamental role played by geometrically necessary crystal defects in controlling mechanical stability and plastic rearrangements of the shell. Designing and controlling particle self-assembly into robust and reliable high-performance smart materials often involves crystalline ordering in curved spaces. Examples include carbon allotropes like graphene, synthetic materials such as colloidosomes, or biological systems like lipid membranes, solid domains on vesicles, or viral capsids. Despite the relevance of these structures, the irreversible deformation and failure of curved crystals is still mostly unexplored. Here, we report simulation results of the mechanical deformation of colloidal crystalline shells that illustrate the subtle role played by geometrically necessary topological defects in controlling plastic yielding and failure. We observe plastic deformation attributable to the migration and reorientation of grain boundary scars, a collective process assisted by the intermittent proliferation of disclination pairs or abrupt structural failure induced by crack nucleating at defects. Our results provide general guiding principles to optimize the structural and mechanical stability of curved colloidal crystals.

Direct Observation of Percolation in the Yielding Transition of Colloidal Glasses

When strained beyond the linear regime, soft colloidal glasses yield to steady-state plastic flow in a way that is similar to the deformation of conventional amorphous solids. Because of the much larger size of the colloidal particles with respect to the atoms comprising an amorphous solid, colloidal glasses allow us to obtain microscopic insight into the nature of the yielding transition, as we illustrate here combining experiments, atomistic simulations, and mesoscopic modeling. Our results unanimously show growing clusters of nonaffine deformation percolating at yielding. In agreement with percolation theory, the spanning cluster is fractal with a fractal dimension d_{f}≃2, and the correlation length diverges upon approaching the critical yield strain. These results indicate that percolation of highly nonaffine particles is the hallmark of the yielding transition in disordered glassy systems.

Current quantization and fractal hierarchy in a driven repulsive lattice gas

Driven lattice gases are widely regarded as the paradigm of collective phenomena out of equilibrium. While such models are usually studied with nearest-neighbor interactions, many empirical driven systems are dominated by slowly decaying interactions such as dipole-dipole and Van der Waals forces. Motivated by this gap, we study the nonequilibrium stationary state of a driven lattice gas with slow-decayed repulsive interactions at zero temperature. By numerical and analytical calculations of the particle current as a function of the density and of the driving field, we identify (i) an abrupt breakdown transition between insulating and conducting states, (ii) current quantization into discrete phases where a finite current flows with infinite differential resistivity, and (iii) a fractal hierarchy of excitations, related to the Farey sequences of number theory. We argue that the origin of these effects is the competition between scales, which also causes the counterintuitive phenomenon that crystalline states can melt by increasing the density.

Wrinkle motifs in thin films

Delamination of coatings and thin films from substrates generates a fascinating variety of patterns, from circular blisters to wrinkles and labyrinth domains, in a way that is not completely understood. We report on large-scale numerical simulations of the universal problem of avoidance and coalescence of delamination wrinkles, focusing on a case study of graphene sheets on patterned substrates. By nucleating and growing wrinkles in a controlled way, we are able to characterize how their interactions, mediated by long-range stress fields, determine their formation and morphology. We also study how the interplay between geometry and stresses drives a universal transition from conformation to delamination when sheets are deposited on particle-decorated substrates. Our results are directly applicable to strain engineering of graphene and also uncover universal phenomena observed at all scales, as for example in geomembrane deposition.On length scales from nanometres to metres, partial adhesion of thin films with substrates generates a fascinating variety of patterns, such as ‘telephone cord’ buckles, wrinkles, and labyrinth domains. Although these patterns are part of everyday experience and are important in industry, they are not completely understood. Here, we report simulation studies of a previously-overlooked phenomenon in which pairs of wrinkles form avoiding pairs, focusing on the case of graphene over patterned substrates. By nucleating and growing wrinkles in a controlled way, we characterize how their morphology is determined by stress fields in the sheet and friction with the substrate. Our simulations uncover the generic behaviour of avoiding wrinkle pairs that should be valid at all scales.

Atomic-Scale Front Propagation at the Onset of Frictional Sliding

Macroscopic frictional sliding emerges from atomic-scale interactions and processes at the contact interface, but bridging the gap between micro and macro scales still remains an unsolved challenge. Direct imaging of the contact surface and simultaneous measurement of stress fields during macroscopic frictional slip revealed the formation of crack precursors, questioning the traditional picture of frictional contacts described in terms of a single degree of freedom. Here we study the onset of frictional slip on the atomic scale by simulating the motion of an aluminum block pushed by a slider on a copper substrate. We show the formation of dynamic slip front propagation and precursory activity that resemble macroscopic observations. The analysis of stress patterns during slip, however, reveals subtle effects due to the lattice structures that hinder a direct application of linear elastic fracture mechanics. Our results illustrate that dynamic front propagation arises already on the atomic scales and shed light on the connections between atomic-scale and macroscopic friction.

Damage Accumulation in Silica Glass Nanofibers

The origin of the brittle-to-ductile transition, experimentally observed in amorphous silica nanofibers as the sample size is reduced, is still debated. Here we investigate the issue by extensive molecular dynamics simulations at low and room temperatures for a broad range of sample sizes, with open and periodic boundary conditions. Our results show that small sample-size enhanced ductility is primarily due to diffuse damage accumulation, that for larger samples leads to brittle catastrophic failure. Surface effects such as boundary fluidization contribute to ductility at room temperature by promoting necking, but are not the main driver of the transition. Our results suggest that the experimentally observed size-induced ductility of silica nanofibers is a manifestation of finite-size criticality, as expected in general for quasi-brittle disordered networks.