arXiv subjects

Giorgia Ciavolella

Publications and source records attributed to Giorgia Ciavolella.

5 recordsLinked to original sources

arXiv2025

Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model

The spread of metastases is a crucial process in which some questions remain unanswered. In this work, we focus on tumor cells circulating in the bloodstream, the so-called Circulating Tumor Cells (CTCs). Our aim is to characterize their trajectories under the influence of hemodynamic and adhesion forces. We focus on already available in vitro measurements performed with a microfluidic device corresponding to the trajectories of CTCs -- without or with different protein depletions -- interacting with an endothelial layer. A key difficulty is the weak knowledge of the fluid velocity that has to be reconstructed. Our strategy combines a differential equation model -- a Poiseuille model for the fluid velocity and an ODE system for the cell adhesion model -- and a robust and well-designed calibration procedure. The parameterized model quantifies the strong influence of fluid velocity on adhesion and confirms the expected role of several proteins in the deceleration of CTCs. Finally, it enables the generation of synthetic cells, even for unobserved experimental conditions, opening the way to a digital twin for flowing cells with adhesion.

q-bio.TO↗

arXiv2024

A model for membrane degradation using a gelatin invadopodia assay

One of the most crucial and lethal characteristics of solid tumors is represented by the increased ability of cancer cells to migrate and invade other organs during the so-called metastatic spread. This is allowed thanks to the production of matrix metalloproteinases (MMPs), enzymes capable of degrading a type of collagen abundant in the basal membrane separating the epithelial tissue from the connective one. In this work, we employ a synergistic experimental and mathematical modelling approach to explore the invasion process of tumor cells. A athematical model composed of reaction-diffusion equations describing the evolution of the tumor cells density on a gelatin substrate, MMPs enzymes concentration and the degradation of the gelatin is proposed. This is completed with a calibration strategy. We perform a sensitivity analysis and explore a parameter estimation technique both on synthetic and experimental data in order to find the optimal parameters that describe the in vitro experiments. A comparison between numerical and experimental solutions ends the work.

q-bio.TO↗

arXiv2023

Effective interface conditions for a porous medium type problem

Motivated by biological applications on tumour invasion through thin membranes, we study a porous-medium type equation where the density of the cell population evolves under Darcy's law, assuming continuity of both the density and flux velocity on the thin membrane which separates two domains. The drastically different scales and mobility rates between the membrane and the adjacent tissues lead to consider the limit as the thickness of the membrane approaches zero. We are interested in recovering the effective interface problem and the transmission conditions on the limiting zero-thickness surface, formally derived by Chaplain et al. (2019), which are compatible with nonlinear generalized Kedem-Katchalsky ones. Our analysis relies on a priori estimates and compactness arguments as well as on the construction of a suitable extension operator which allows to deal with the degeneracy of the mobility rate in the membrane, as its thickness tends to zero.

math.AP↗

arXiv2022

Existence of a global weak solution for a reaction-diffusion problem with membrane conditions

Several problems, issued from physics, biology or the medical science, lead to parabolic equations set in two sub-domains separated by a membrane with selective permeability to specific molecules. The corresponding boundary conditions, describing the flow through the membrane, are compatible with mass conservation and energy dissipation, and are called the Kedem-Katchalsky conditions. Additionally, in these models, written as reaction-diffusion systems, the reaction terms have a quadratic behaviour. M. Pierre and his collaborators have developed a complete $L^1$ theory for reaction-diffusion systems with different diffusions. Here, we adapt this theory to the membrane boundary conditions and prove the existence of weak solutions when the initial data has only $L^1$ regularity using the truncation method for the nonlinearities. In particular, we establish several estimates as the $W^{1,1}$ regularity of the solutions. Also, a crucial step is to adapt the fundamental $L^2$ (space, time) integrability lemma to our situation.

math.AP↗

arXiv2022

Effect of a membrane on diffusion-driven Turing instability

Biological, physical, medical, and numerical applications involving membrane problems on different scales are numerous. We propose an extension of the standard Turing theory to the case of two domains separated by a permeable membrane. To this aim, we study a reaction-diffusion system with zero-flux boundary conditions on the external boundary and Kedem-Katchalsky membrane conditions on the inner membrane. We use the same approach as in the classical Turing analysis but applied to membrane operators. The introduction of a diagonalization theory for compact and self-adjoint membrane operators is needed. Here, Turing instability is proven with the addition of new constraints, due to the presence of membrane permeability coefficients. We perform an explicit one-dimensional analysis of the eigenvalue problem, combined with numerical simulations, to validate the theoretical results. Finally, we observe the formation of discontinuous patterns in a system which combines diffusion and dissipative membrane conditions, varying both diffusion and membrane permeability coefficients. The case of a fast reaction-diffusion system is also considered.

math.AP↗