title: Dynamic cellular finite-element method for modelling large-scale cell migration and proliferation under the control of mechanical and biochemical cues: a study of re-epithelialization.
abstract: Computational modelling of cells can reveal insight into the mechanisms of the important processes of tissue development. However, current cell models have limitations and are challenged to model detailed changes in cellular shapes and physical mechanics when thousands of migrating and interacting cells need to be modelled. Here we describe a novel dynamic cellular finite-element model (DyCelFEM), which accounts for changes in cellular shapes and mechanics. It also models the full range of cell motion, from movements of individual cells to collective cell migrations. The transmission of mechanical forces regulated by intercellular adhesions and their ruptures are also accounted for. Intra-cellular protein signalling networks controlling cell behaviours are embedded in individual cells. We employ DyCelFEM to examine specific effects of biochemical and mechanical cues in regulating cell migration and proliferation, and in controlling tissue patterning using a simplified re-epithelialization model of wound tissue. Our results suggest that biochemical cues are better at guiding cell migration with improved directionality and persistence, while mechanical cues are better at coordinating collective cell migration. Overall, DyCelFEM can be used to study developmental processes when a large population of migrating cells under mechanical and biochemical controls experience complex changes in cell shapes and mechanics.
authors.affiliation: Department of Bioengineering, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jieling
authors.identifier: 0000-0002-9801-2434
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Theoretical Biology and Biophysics (T-6), Center for Nonlinear Studies (CNLS), Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Youfang
authors.identifier: 0000-0002-5880-0006
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Luisa A
authors.initials: LA
authors.lastname: DiPietro
authors.affiliation: Department of Bioengineering, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA jliang@uic.edu.
authors.forename: Jie
authors.identifier: 0000-0002-2773-6427
authors.initials: J
authors.lastname: Liang
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D008954:Models, Biological; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology
keywords: cell migration and proliferation; cellular mechanics; collective cell migration; dynamic cellular finite-element model; re-epithelialization; tissue modelling