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Pasquale Ciarletta

Publications and source records attributed to Pasquale Ciarletta.

16 recordsLinked to original sources

Modeling the prion protein-mediated transport of extracellular vesicles on the neuron surface

Neurodegenerative diseases are among the leading causes of global mortality, characterized by the progressive deterioration of specific neuron populations, ultimately leading to cognitive decline and dementia. Extracellular vesicles (EVs) are believed to play a role in the early stages of these diseases, acting as carriers of pathogens and contributing to neuroinflammation and disease propagation. This study presents a mathematical model aimed at characterizing the movement of EVs bearing prion protein (PrP) on their surface along neuronal surfaces. The model, informed by experimental data, investigates the influence of PrP and actin polymerization on EV transport dynamics and explores the possible interplay between passive and active mechanisms. EVs isolated from non-human astrocytes were analyzed under three conditions: untreated control (Ctrl), neurons treated with Cytochalasin D (CytoD-HN), and EVs treated with Cytochalasin D (CytoD-EV). The mathematical model is data-driven, testing different hypotheses regarding the underlying transport mechanisms. In the CytoD-EV dataset, EV movement was modeled using a flashing Brownian ratchet to represent directed motion. For active transport in the CytoD-HN set, a symmetric periodic potential was used to describe EV rolling along the neuron surface. The Ctrl scenario incorporates both mechanisms, reflecting a more complex transport behavior. A sensitivity analysis and comparison between numerical predictions and experimental data suggest that the model effectively captures key features of EV motion, providing a quantitative framework to interpret different transport regimes. While some variability remains, the approach offers a promising basis for future investigations into the role of cytoskeletal dynamics in EV-mediated disease propagation.

physics.bio-ph

The elastic stored energy of initially strained, or stressed, materials: restrictions and third-order expansions

A large variety of materials, widely encountered both in engineering applications and in the biological realm, are characterised by a non-vanishing internal stress distribution, even in the absence of external deformations or applied forces. These initial stresses are due to initial strains or microstructural changes, such as thermal expansion, manufacturing processes, volumetric growth, remodelling, etc. A common constitutive choice for modelling such materials extends the classical approach in the field theory of continuum mechanics to include, explicitly, the initial stress or strain in the elastic stored energy function. Here, we discuss why these energy functions need to satisfy some restrictions to avoid unphysical behaviours, such as non-conservation of energy, {and we derive the required restrictions from the classical assumptions of elasticity.} To illustrate their need, we perform a rigorous asymptotic expansion for proving that these restrictions on stored energy functions that depend on the strain and initial stress are required for consistency with strain energy functions of classical third-order weakly nonlinear elasticity.

cond-mat.soft

Tunable morphing of electroactive dielectric-elastomer balloons

Designing smart devices with tunable shapes has important applications in industrial manufacture. In this paper, we investigate the nonlinear deformation and the morphological transitions between buckling, necking, and snap-through instabilities of layered DE balloons in response to an applied radial voltage and an inner pressure. We propose a general mathematical theory of nonlinear electro-elasticity able to account for finite inhomogeneous strains provoked by the electro-mechanical coupling. We investigate the onsets of morphological transitions of the spherically symmetric balloons using the surface impedance matrix method. Moreover, we study the nonlinear evolution of the bifurcated branches through finite element numerical simulations. Our analysis demonstrates the possibility to design tunable DE spheres, where the onset of buckling and necking can be controlled by geometrical and mechanical properties of the passive elastic layers. Relevant applications include soft robotics and mechanical actuators.

cond-mat.soft

Flattened and wrinkled encapsulated droplets: Shape-morphing induced by gravity and evaporation

We report surprising morphological changes of suspension droplets (containing class II hydrophobin protein HFBI from Trichoderma reesei and water) as they evaporate with a contact line pinned on a rigid solid substrate. Both pendant and sessile droplets display the formation of an encapsulating elastic film as the bulk concentration of solute reaches a critical value during evaporation, but the morphology of the droplet varies significantly: for sessile droplets, the elastic film ultimately crumples in a nearly flattened area close to the apex while in pendant droplets, circumferential wrinkling occurs close to the contact line. These different morphologies are understood through a gravito-elasto-capillary model that predicts the droplet morphology and the onset of shape changes, as well as showing that the influence of the direction of gravity remains crucial even for very small droplets (where the effect of gravity can normally be neglected). The results pave the way to control droplet shape in several engineering and biomedical applications.

cond-mat.soft

Morphomechanical model of the torsional c-looping in the embryonic heart

Before septation processes shape its four chambers, the embryonic heart is a straight tube that spontaneously bends and twists breaking the left-right symmetry. In particular, the heart tube is subjected to a cell remodelling inducing ventral bending and dextral torsion during the c-looping phase. In this work we propose a morphomechanical model for the torsion of the heart tube, that behaves as a nonlinear elastic body. We hypothesize that this spontaneous looping can be modeled as a mechanical instability due to accumulation of residual stresses induced by the geometrical frustration of tissue remodelling, which mimics the cellular rearrangement within the heart tube. Thus, we perform a linear stability analysis of the resulting nonlinear elastic boundary value problem to determine the onset of c-looping as a function of the aspect ratios of the tube and of the internal remodelling rate. We perform numerical simulations to study the fully nonlinear morphological transition, showing that the soft tube develops a realistic self-contacting looped shape in the physiological range of geometrical parameters.

cond-mat.soft

Torsion instability of soft solid cylinders

The application of pure torsion to a long and thin cylindrical rod is known to provoke a twisting instability, evolving from an initial kink to a knot. In the torsional parallel-plate rheometry of stubby cylinders, the geometrical constraints impose zero displacement of the axis of the cylinder, preventing the occurrence of such twisting instability. Under these experimental conditions, wrinkles occur on the cylinder's surface at a given critical angle of torsion. Here we investigate this subclass of elastic instability--which we call torsion instability--of soft cylinders subject to a combined finite axial stretch and torsion, by applying the theory of incremental elastic deformation superimposed on finite strains. We formulate the incremental boundary elastic problem in the Stroh differential form, and use the surface impedance method to build a robust numerical procedure for deriving the marginal stability curves. We present the results for a Mooney-Rivlin material and study the influence of the material parameters on the elastic bifurcation.

cond-mat.soft

Morphology of residually-stressed tubular tissues: Beyond the elastic multiplicative decomposition

Many interesting shapes appearing in the biological world are formed by the onset of mechanical instability. In this work we consider how the build-up of residual stress can cause a solid to buckle. In all past studies a fictitious (virtual) stress-free state was required to calculate the residual stress. In contrast, we use a model which is simple and allows the prescription of any residual stress field. We specialize the analysis to an elastic tube subject to a two-dimensional residual stress, and find that incremental wrinkles can appear on its inner or its outer face, depending on the location of the highest value of the residual hoop stress. We further validate the predictions of the incremental theory with finite element simulations, which allow us to go beyond this threshold and predict the shape, number and amplitude of the resulting creases.

cond-mat.soft

Learning patient-specific parameters for a diffuse interface glioblastoma model from neuroimaging data

Parameters in mathematical models for glioblastoma multiforme (GBM) tumour growth are highly patient specific. Here we aim to estimate parameters in a Cahn-Hilliard type diffuse interface model in an optimised way using model order reduction (MOR) based on proper orthogonal decomposition (POD). Based on snapshots derived from finite element simulations for the full order model (FOM) we use POD for dimension reduction and solve the parameter estimation for the reduced order model (ROM). Neuroimaging data are used to define the highly inhomogeneous diffusion tensors as well as to define a target functional in a patient specific manner. The reduced order model heavily relies on the discrete empirical interpolation method (DEIM) which has to be appropriately adapted in order to deal with the highly nonlinear and degenerate parabolic PDEs. A feature of the approach is that we iterate between full order solves with new parameters to compute a POD basis function and sensitivity based parameter estimation for the ROM problems. The algorithm is applied using neuroimaging data for two clinical test cases and we can demonstrate that the reduced order approach drastically decreases the computational effort.

math.NA

The self-organised, non-equilibrium dynamics of spontaneous cancerous buds

Tissue self-organization into defined and well-controlled three-dimensional structures is essential during development for the generation of organs. A similar, but highly deranged process might also occur during the aberrant growth of cancers, which frequently display a loss of the orderly structures of the tissue of origin, but retain a multicellular organization in the form of spheroids, strands, and buds. The latter structures are often seen when tumors masses switch to an invasive behavior into surrounding tissues. However, the general physical principles governing the self-organized architectures of tumor cell populations remain by and large unclear. In this work, we perform in-vitro experiments to characterize the growth properties of glioblastoma budding emerging from monolayers. Using a theoretical model and numerical tools here we find that such a topological transition is a self-organised, non-equilibrium phenomenon driven by the trade--off of mechanical forces and physical interactions exerted at cell-cell and cell-substrate adhesions. Notably, the unstable disorder states of uncontrolled cellular proliferation macroscopically emerge as complex spatio--temporal patterns that evolve statistically correlated by a universal law.

q-bio.CB

On the existence of elastic minimizers for initially stressed materials

A soft solid is said to be initially stressed if it is subjected to a state of internal stress in its unloaded reference configuration. Developing a sound mathematical framework to model initially stressed solids in nonlinear elasticity is key for many applications in engineering and biology. This work investigates the links between the existence of elastic minimizers and the constitutive restrictions for initially stressed materials subjected to finite deformations. In particular, we consider a subclass of constitutive responses in which the strain energy density is taken as a scalar valued function of both the deformation gradient and the initial stress tensor. The main advantage of this approach is that the initial stress tensor belongs to the group of the divergence-free symmetric tensors satisfying the boundary condition in any given reference configuration. However, it is still unclear which physical restrictions must be imposed for the well-posedness of this elastic problem. Assuming that the constitutive response depends on the choice of the reference configuration only through the initial stress tensor, under given conditions we prove the local existence of a relaxed state given by an implicit tensor function of the initial stress distribution. This tensor function is generally not unique, and can be transformed accordingly to the symmetry group of the material at fixed initial stresses. These results allow to extend Ball's existence theorem of elastic minimizers for the proposed constitutive choice of initially stressed materials.

cond-mat.soft

Morpho-elastic model of the tortuous tumour vessels

Solid tumours have the ability to assemble their own vascular network for optimizing their access to the vital nutrients. These new capillaries are morphologically different from normal physiological vessels. In particular, they have a much higher spatial tortuosity forcing an impaired flow within the peritumoral area. This is a major obstacle for the efficient delivery of antitumoral drugs. This work proposes a morpho-elastic model of the tumour vessels. A tumour capillary is considered as a growing hyperelastic tube that is spatially constrained by a linear elastic environment, representing the interstitial matter. We assume that the capillary is an incompressible neo-Hookean material, whose growth is modeled using a multiplicative decomposition of the deformation gradient. We study the morphological stability of the capillary by means of the method of incremental deformations superposed on finite strains, solving the corresponding incremental problem using the Stroh formulation and the impedance matrix method. The incompatible axial growth of the straight capillary is found to control the onset of a bifurcation towards a tortuous shape. The post-buckling morphology is studied using a mixed finite element formulation in the fully nonlinear regime. The proposed model highlights how the geometrical and the elastic properties of the capillary and the surrounding medium concur to trigger the loss of marginal stability of the straight capillary and the nonlinear development of its spatial tortuosity.

cond-mat.soft

Shape transitions in a soft incompressible sphere with residual stresses

Residual stresses may appear in elastic bodies due to the formation of misfits in the micro-structure, driven by plastic deformations, thermal or growth processes. They are especially widespread in living matter, resulting from the dynamic remodelling processes aiming at optimizing the overall structural response to environmental physical forces. From a mechanical viewpoint, residual stresses are classically modelled through the introduction of a virtual incompatible state that collects the local relaxed states around each material point. In this work, we instead employ an alternative approach based on a strain energy function that constitutively depends only on the deformation gradient and the residual stress tensor. In particular, our objective is to study the morphological stability of an incompressible sphere, made of a neo-Hookean material and subjected to given distributions of residual stresses. Firstly, we perform a linear stability analysis on the pre-stressed solid sphere using the method of incremental deformations. The marginal stability conditions are given as a function of a control parameter, being the dimensionless variable that represents the characteristic intensity of the residual stresses. Secondly, we perform finite element simulations using a mixed formulation in order to investigate the post-buckling morphology in the fully nonlinear regime. Considering different distributions of the residual stresses, we find that different morphological transitions occur around the material domain where the hoop residual stress reaches its maximum compressive value. The results provide useful guidelines in order to design morphable soft spheres, for example by controlling the residual stresses through active deformations. They finally suggest a viable solution for the nondestructive characterization of residual stresses in soft tissues, such as solid tumors.

cond-mat.soft

Rayleigh-Taylor instability in soft elastic layers

This work investigates the morphological stability of a soft body composed of two heavy elastic layers, attached to a rigid surface and subjected only to the bulk gravity force. Using theoretical and computational tools, we characterize the selection of different patterns as well as their nonlinear evolution, unveiling the interplay between elastic and geometric effects for their formation. Unlike similar gravity-induced shape transitions in fluids, as the Rayleigh-Taylor instability, we prove that the nonlinear elastic effects saturate the dynamic instability of the bifurcated solutions, displaying a rich morphological diagram where both digitations and stable wrinkling can emerge. The results of this work provide important guidelines for the design of novel soft systems with tunable shapes, with several applications in engineering sciences.

cond-mat.soft

A new restriction for initially stressed elastic solids

We introduce a fundamental restriction on the strain energy function and stress tensor for initially stressed elastic solids. The restriction applies to strain energy functions $W$ that are explicit functions of the elastic deformation gradient $\mathbf{F}$ and initial stress $\boldsymbol τ$, i.e. $W:= W(\mathbf F, \boldsymbol τ)$. The restriction is a consequence of energy conservation and ensures that the predicted stress and strain energy do not depend upon an arbitrary choice of reference configuration. We call this restriction: initial stress reference independence (ISRI). It transpires that almost all strain energy functions found in the literature do not satisfy ISRI, and may therefore lead to unphysical behaviour, which we illustrate via a simple example. To remedy this shortcoming we derive three strain energy functions that do satisfy the restriction. We also show that using initial strain (often from a virtual configuration) to model initial stress leads to strain energy functions that automatically satisfy ISRI. Finally, we reach the following important result: ISRI reduces the number of unknowns of the linear stress tensor of initially stressed solids. This new way of reducing the linear stress may open new pathways for the non-destructive determination of initial stresses via ultrasonic experiments, among others.

cond-mat.soft

Initial Stress Symmetry and Applications in Elasticity

An initial stress within a solid can arise to support external loads or from processes such as thermal expansion in inert matter or growth and remodelling in living materials. For this reason it is useful to develop a mechanical framework of initially stressed solids irrespective of how this stress formed. An ideal way to do this is to write the free energy density $Ψ= Ψ(\boldsymbol F, \boldsymbol τ)$ in terms of initial stress $\boldsymbol τ$ and the elastic deformation gradient $\boldsymbol F$. In this paper we present a new constitutive condition for initially stressed materials, which we call the initial stress symmetry (ISS). We focus on two consequences of this symmetry. First we examine how ISS restricts the free energy density $Ψ= Ψ(\boldsymbol F, \boldsymbol τ) $ and present two examples of $Ψ(\boldsymbol F, \boldsymbol τ)$ that satisfy ISS. Second we show that the initial stress can be derived from the Cauchy stress and the elastic deformation gradient. To illustrate we take an example from biomechanics and calculate the optimal Cauchy stress within an artery subjected to internal pressure. We then use ISS to derive the optimal target residual stress for the material to achieve after remodelling.

cond-mat.soft

Shear instability in skin tissue

We propose two toy-models to describe, predict, and interpret the wrinkles appearing on the surface of skin when it is sheared. With the first model, we account for the lines of greatest tension present in human skin by subjecting a layer of soft tissue to a pre-stretch, and for the epidermis by endowing one of the layer's faces with a surface tension. For the second model, we consider an anisotropic model for the skin, to reflect the presence of stiff collagen fibres in a softer elastic matrix. In both cases, we find an explicit bifurcation criterion, linking geometrical and material parameters to a critical shear deformation accompanied by small static wrinkles, with decaying amplitudes normal to the free surface of skin.

cond-mat.soft