title: An agent-based model for elasto-plastic mechanical interactions between cells, basement membrane and extracellular matrix.
abstract: The basement membrane (BM) and extracellular matrix (ECM) play critical roles in developmental and cancer biology, and are of great interest in biomathematics. We introduce a model of mechanical cell-BM-ECM interactions that extends current (visco)elastic models (e.g. [8,16]), and connects to recent agent-based cell models (e.g. [2,3,20,26]). We model the BM as a linked series of Hookean springs, each with time-varying length, thickness, and spring constant. Each BM spring node exchanges adhesive and repulsive forces with the cell agents using potential functions. We model elastic BM-ECM interactions with analogous ECM springs. We introduce a new model of plastic BM and ECM reorganization in response to prolonged strains, and new constitutive relations that incorporate molecular-scale effects of plasticity into the spring constants. We find that varying the balance of BM and ECM elasticity alters the node spacing along cell boundaries, yielding a nonuniform BM thickness. Uneven node spacing generates stresses that are relieved by plasticity over long times. We find that elasto-viscoplastic cell shape response is critical to relieving uneven stresses in the BM. Our modeling advances and results highlight the importance of rigorously modeling of cell-BM-ECM interactions in clinically important conditions with significant membrane deformations and time-varying membrane properties, such as aneurysms and progression from in situ to invasive carcinoma.
authors: Politecnico di Torino, Torino, 10124, Italy. gianluca.dantonio@studenti.polito.it
authors: Gianluca
authors: G
authors: D'Antonio
authors: Paul
authors: P
authors: Macklin
authors: Luigi
authors: L
authors: Preziosi
mesh_terms: D000465:Algorithms; D001485:Basement Membrane / Q000502:physiology*; D002138:Calibration; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D003198:Computer Simulation; D004548:Elasticity; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D014783:Viscosity
chemical_list: D016326:Extracellular Matrix Proteins; D008024:Ligands