Branching instability in expanding bacterial colonies

International audienceSelf-organization in developing living organisms relies on the capability of cells to duplicate and perform a collective motion inside the surrounding environment. Chemical and mechanical interactions coordinate such a cooperative behaviour, driving the dynamical evolution of the macroscopic system. In this work, we perform an analytical and computational analysis to study pattern formation during the spreading of an initially circular bacterial colony on a Petri dish. The continuous mathematical model addresses the growth and the chemotactic migration of the living monolayer, together with the diffusion and consumption of nutrients in the agar. The governing equations contain four dimensionless parameters, accounting for the interplay among the chemotactic response, the bacteria-substrate interaction and the experimental geometry. The spreading colony is found to be always linearly unstable to perturbations of the interface, whereas branching instability arises in finite-element numerical simulations. The typical length scales of such fingers, which align in the radial direction and later undergo further branching, are controlled by the size parameters of the problem, whereas the emergence of branching is favoured if the diffusion is dominant on the chemotaxis. The model is able to predict the experimental morphologies, confirming that compact (resp. branched) patterns arise for fast (resp. slow) expanding colonies. Such results, while providing new insights into pattern selection in bacterial colonies, may finally have important applications for designing controlled patterns

Behavior of cell aggregates under force-controlled compression

In this paper we study the mechanical behavior of multicellular aggregates under compressive loads and subsequent releases. Some analytical properties of the solution are discussed and numerical results are presented for a compressive test under constant force imposed on a cylindrical specimen. The case of a cycle of compressions at constant force and releases is also considered. We show that a steady state configuration able to bear the load is achieved. The analytical determination of the steady state value allows to obtain mechanical parameters of the cellular structure that are not estimable from creep tests at constant stres

Cell and cell-aggregate mechanics: remodelling, growth and interaction with the extracellular environment.

The scope of this dissertation is to give a contribution to the understanding of the mathematical description of cell and cellular aggregate mechanics, focusing on remodelling and growth processes which occur inside living structures and on the interactions among cells and the extracellular environment, during the process of cell migration

Cell orientation under stretch: Stability of a linear viscoelastic model

The sensitivity of cells to alterations in the microenvironment and in particular to external mechanical stimuli is significant in many biological and physiological circumstances. In this regard, experimental assays demonstrated that, when a monolayer of cells cultured on an elastic substrate is subject to an external cyclic stretch with a sufficiently high frequency, a reorganization of actin stress fibres and focal adhesions happens in order to reach a stable equilibrium orientation, characterized by a precise angle between the cell major axis and the largest strain direction. To examine the frequency effect on the orientation dynamics, we propose a linear viscoelastic model that describes the coupled evolution of the cellular stress and the orientation angle. We find that cell orientation oscillates tending to an angle that is predicted by the minimization of a very general orthotropic elastic energy, as confirmed by a bifurcation analysis. Moreover, simulations show that the speed of convergence towards the predicted equilibrium orientation presents a changeover related to the viscous–elastic transition for viscoelastic materials. In particular, when the imposed oscillation period is lower than the characteristic turnover rate of the cytoskeleton and of adhesion molecules such as integrins, reorientation is significantly faster

Foreword to the Special Issue in honour of Prof. Luigi Preziosi “Nonlinear mechanics: The driving force of modern applied and industrial mathematics”

Mathematical modelling is a discipline pledged to identify problems, which may arise from virtually any branch of the human knowledge, and formalise them in the language of mathematics by developing suitable methodologies of investigation. To pursue its goals, modelling must build connections with other mathematical sciences and, in particular, with numerics. Three major examples of the efficiency of such combination are industrial mathematics, mathematical biology and biomechanics. At first sight, industrial mathematics is a branch of applied mathematics focusing on problems that come from industry and it aims at determining solutions relevant to manufacturing. Some relevant examples are petroleum engineering, hydrogeology, and the description of sand dynamics in the neighbourhood of railways in desert zones. On the other hand, the adoption of mathematics to formalise problems of biological relevance has attracted scientists working on population dynamics, epidemiology and related fields. Moreover, a strong impact has been given by the combination of modelling with the mechanics of biological tissues, thereby giving rise to biomechanics. Few examples in this respect are the mechanics of cell motion and migration, which relate to kinetic theories, the mechanics of the interactions between cells and the extracellular matrix, the conversion of mechanical signals into chemical stimuli, and "mathematical oncology". Since it is not possible to present a theoretical corpus of all that, the aim of the present special issue is to put together a list of outstanding scientific papers giving clear connections among nonlinear mechanics, industrial mathematics, biomathematics, biomechanics and kinetic theories, in different fields of interest. This special issue of IJNLM is the Festschrift celebrating the 60th birthday of Luigi Preziosi, whose research is a recognised example of how mechanics may be the fuel for interesting applied mathematics

Influence of nucleus deformability on cell entry into cylindrical structures

The mechanical properties of cell nuclei have been demonstrated to play a fundamental role in cell movement across extracellular networks and micro-channels. In this work, we focus on a mathematical description of a cell entering a cylindrical channel composed of extracellular matrix. An energetic approach is derived in order to obtain a necessary condition for which cells enter cylindrical structures. The nucleus of the cell is treated either (i) as an elastic membrane surrounding a liquid droplet or (ii) as an incompressible elastic material with Neo-Hookean constitutive equation. The results obtained highlight the importance of the interplay between mechanical deformability of the nucleus and the capability of the cell to establish adhesive bonds and generate active forces in the cytoskeleton due to myosin action

Modelling and simulation of anisotropic growth in brain tumours through poroelasticity: A study of ventricular compression and therapeutic protocols

Malignant brain tumours represent a significant medical challenge due to their aggressive nature and unpredictable locations. The growth of a brain tumour can result in a mass effect, causing compression and displacement of the surrounding healthy brain tissue and possibly leading to severe neurological complications. In this paper, we propose a multiphase mechanical model for brain tumour growth that quantifies deformations and solid stresses caused by the expanding tumour mass and incorporates anisotropic growth influenced by brain fibres. We employ a sharp interface model to simulate localised, noninvasive solid brain tumours, which are those responsible for substantial mechanical impact on the surrounding healthy tissue. By using patient-specific imaging data, we create realistic three-dimensional brain geometries and accurately represent ventricular shapes, to evaluate how the growing mass may compress and deform the cerebral ventricles. Another relevant feature of our model is the ability to simulate therapeutic protocols, facilitating the evaluation of treatment efficacy and guiding the development of personalized therapies for individual patients. Overall, our model allows to make a step towards a deeper analysis of the complex interactions between brain tumours and their environment, with a particular focus on the impact of a growing cancer on healthy tissue, ventricular compression, and therapeutic treatment

A non local model for cell migration in response to mechanical stimuli

Cell migration is one of the most studied phenomena in biology since it plays a fundamental role in many physiological and pathological processes such as morphogenesis, wound healing and tumorigenesis. In recent years, researchers have performed experiments showing that cells can migrate in response to mechanical stimuli of the substrate they adhere to. Motion toward regions of the substrate with higher stiffness is called durotaxis, while motion guided by the stress or the deformation of the substrate itself is called tensotaxis. Unlike chemotaxis (i.e. the motion in response to a chemical stimulus), these migratory processes are not yet fully understood from a biological point of view. In this respect, we present a mathematical model of single-cell migration in response to mechanical stimuli, in order to simulate these two processes. Specifically, the cell moves by changing its direction of polarization and its motility according to material properties of the substrate (e.g., stiffness) or in response to proper scalar measures of the substrate strain or stress. The equations of motion of the cell are non-local integro-differential equations, with the addition of a stochastic term to account for random Brownian motion. The mechanical stimulus to be integrated in the equations of motion is defined according to experimental measurements found in literature, in the case of durotaxis. Conversely, in the case of tensotaxis, substrate strain and stress are given by the solution of the mechanical problem, assuming that the extracellular matrix behaves as a hyperelastic Yeoh's solid. In both cases, the proposed model is validated through numerical simulations that qualitatively reproduce different experimental scenarios

The Effect of Cell Death on the Stability of a Growing Biofilm

In this paper, we investigate the role of cell death in promoting pattern formation within bacterial biofilms. To do this we utilise an extension of the model proposed by Dockery and Klapper [13], and consider the effects of two distinct death rates. Equations describing the evolution of a moving biofilm interface are derived, and properties of steady state solutions are examined. In particular, a comparison of the planar behaviour of the biofilm interface in the different cases of cell death is investigated. Linear stability analysis is carried out at steady state solutions of the interface, and it is shown that, under certain conditions, instabilities may arise. Analysis determines that, while the emergence of patterns is a possibility in `deep’ biofilms, it is unlikely that pattern formation will arise in `shallow’ biofilms