A Model for Membrane Degradation Using a Gelatin Invadopodia Assay

Bull Math Biol. 2024 Feb 12;86(3):30. doi: 10.1007/s11538-024-01260-w.

Abstract

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 mathematical 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.

Keywords: Finite difference methods; Parameter estimation; Reaction-diffusion equations; Sensitivity analysis; Tumour degradation and invasion models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Matrix / pathology
  • Gelatin / metabolism
  • Humans
  • Mathematical Concepts
  • Matrix Metalloproteinases / metabolism
  • Models, Biological
  • Neoplasm Invasiveness / pathology
  • Podosomes* / metabolism
  • Podosomes* / pathology

Substances

  • Gelatin
  • Matrix Metalloproteinases