Mathematics of collective cell migration in electric field
Abstract
Objectives: Cell migration is a fundamental process underlying wound healing and other physiological phenomena. Two aspects of cell migration are physical motility (ability of the cell to generate forces and movements) and directional sensing (ability to migrate in the direction of chemical or electrical cues Ð chemotaxis and galvanotaxis, respectively). While there is some progress in research on individual cell motility and chemotaxis, quantitative understanding of galvanotaxis and of directional collective migration is lacking. There are four principal questions to be answered: How does a single motile cell integrates its mechanical apparatus, electric field sensor and biochemical regulatory pathways? How do multiple cells interact mechanically in a cohesive group? Is there a collective decision making about the direction of locomotion? How can we simulate the multiscale cell migration without losing information about sub-cellular mechanochemical processes? To answer these questions, the PI will develop models of biophysical mechanism for electrical field sensing, of biochemical mechanism of relaying the electric signal to the mechanical machinery of the cell, and couple the electric, chemical and mechanical models to develop and test predictive multiscale model of the directionally migrating cell. The resulting model will be numerically simulated and tested in collaboration with experimentalists. Then, the PI will develop a computational model of collective migration of cohesive groups of tens and hundreds of mechanically and chemically coupled cells. Importantly, cells mechanics and electric sensing will depend on the position in the group. Methods to be employed: The PI will develop multiscale models for directional cell migration consisting of coupled mechanical, biochemical and electrical sensing modules. For understanding the electrical sensing, multiple alternative models of ion electrodiffusion/convection will be developed and simulated using the Immersed Boundary method. These activities will result in a free boundary problem that will be solved numerically using the level set method. Simulation of collective cell migration presents significant computational challenge. The PI will develop a novel parallel algorithm for hierarchical simulation of the overlapping multiple free boundary problem. Optimized kinetic decomposition algorithm will be used to simulate collective migration of the cohesive cell groups. All simulation results will produce predictions that will be tested in collaboration with experimentalists. Significance of the proposed activity to the advancement of knowledge: The proposed research will result in quantitative understanding of the mechanisms of galvanotaxis and collective directional cell migration. More broadly, four significant deliverables will be: 1) quantitative models needed to understand and control wound healing; 2) better understanding of electromagnetic effects on human tissues; 3) bridging of micro- and macro-scales in general problem of collective movements of groups of organisms; 4) new effective numerical methods for mathematical biology. Even more broadly, the results will shed light on fundamental biological laws of redundancy, noise optimization and feedback coupling underlying robustness and multitasking characteristic for biological systems.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 11, 2018
- Source ID
- W911NF1710417
Entities
People
- Alex Mogilner
Organizations
- Army Contracting Command
- New York University
- United States Army