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

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

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

Reduced adhesion between cells and substrate confers selective advantage in bacterial colonies

Microbial colonies cultured on agar Petri dishes have become a model system to study biological evolution in populations expanding in space. Processes such as clonal segregation and gene surfing have been shown to be affected by interactions between microbial cells and their environment. In this work we investigate the role of mechanical interactions such as cell-surface adhesion. We compare two strains of the bacterium E. coli: a wild-type strain and a "shaved" strain that adheres less to agar. We show that the shaved strain has a selective advantage over the wild type: although both strains grow with the same rate in liquid media, the shaved strain produces colonies that expand faster on agar. This allows the shaved strain outgrow the wild type when both strains compete for space. We hypothesise that, in contrast to a more common scenario in which selective advantage results from increased growth rate, the higher fitness of the shaved strain is caused by reduced adhesion and friction with the agar surface.Comment: 7 pages, 7 figures, submitted to the EPL Special Issue "Evolutionary modeling and experimental evolution

A Cellular Potts Model simulating cell migration on and in matrix environments

Cell migration on and through extracellular matrix plays a critical role in a wide variety of physiological and pathological phenomena, and in scaffold-based tissue engineering. Migration is regulated by a number of extracellular matrix- or cell-derived biophysical parameters, such as matrix fiber orientation, gap size, and elasticity, or cell deformation, proteolysis, and adhesion. We here present an extended Cellular Potts Model (CPM) able to qualitatively and quantitatively describe cell migratory phenotype on both two-dimensional substrates and within three-dimensional environments, in a close comparison with experimental evidence. As distinct features of our approach, the cells are represented by compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the extracellular matrix is composed of a fibrous mesh and of a homogeneous fluid. Our model provides a strong correlation of the directionality of migration with the topological ECM distribution and, further, a biphasic dependence of migration on the matrix density, and in part adhesion, in both two-dimensional and three-dimensional settings. Moreover, we demonstrate that the directional component of cell movement is strongly correlated with the topological distribution of the ECM fibrous network. In the three-dimensional networks, we also investigate the effects of the matrix mechanical microstructure, observing that, at a given distribution of fibers, cell motility has a subtle bimodal relation with the elasticity of the scaffold. Finally, cell locomotion requires deformation of the cell's nucleus and/or cell-derived proteolysis of steric fibrillar obstacles within rather rigid matrices characterized by small pores, not, however, for sufficiently large pores. In conclusion, we here propose a mathematical modeling approach that serves to characterize cell migration as a biological phenomen in health, disease and tissue engineering applications. The research that led to the present paper was partially supported by a grant of the group GNFM of INdA

Using mathematical modelling as a virtual microscope to support biomedical research

This chapter will explain what kind of support mathematics can give to biology and medicine. In order to explain the concepts in practice cell migration is used as a specific example. This phenomenon is of great biomedical interest because it is a fundamental phenomenon both in physiological (e.g. wound healing, immune response) and pathological processes (e.g. chronic inflammation, detachment of metastasis and related tissue invasion). Also a key feature of any artificial system aimed at mimicking biological structures is to allow and enhance cell migration on or inside it. At the same time anti-cancer treatment can become more efficient blocking cell's capability to migrate towards distant sites and invade different organ