Multiscale Models of Cell Motility
Abstract
The objective of this proposal is to develop multiscale models in time and spatial coordinates in order to uncover the fundamental laws governing cellular motility. The proposal takes a two-pronged approach to answer two important questions remaining about cellular motility: 1) How does spatial compartmentalization of signaling (plasma membrane versus cytoplasm) affect motility responses? 2) How does cell shape change during cell motility? To answer these questions, Project 1 has to do with spatial compartmentalization of signaling reactions. Current models consider only solutions exhibiting little spatial structure. To remedy this problem, the assumption of a well-mixed system will be replaced by considering a reaction-diffusion system with the kinetics of the well-mixed model. Using this new model, the following studies will be carried out: a) Identification of the stability properties of this minimal cell polarity model. b) Extension of the analysis to a single-compartment model in two spatial dimensions. c) Extension to a 1D spatial model with two compartments (approximating a cross-section of the cell adjacent to the plasma membrane). d) Extension of the two-compartment model to two spatial dimensions. Project 2 has to do with change in cell shape in response to actin remodeling during cell motility. The following studies in this area will be carried out: a) Development of 1D and 2D models of cell motility in fixed coordinates, including appropriate biochemical kinetics in a well-mixed model. b) Development of a suite of hybrid simulation algorithms in which slow reactions and fluxes are handled through exact stochastic simulation and their fast counterparts are treated partially deterministically through chemical Langevin equations. c) Employment of upscaling techniques to derive effective equations for the average concentrations of key proteins involved in cell motility. d) To handle dynamic changes in cell shape
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 27, 2017
- Source ID
- W911NF1610411
Entities
People
- Padmini Rangamani
Organizations
- Army Contracting Command
- United States Army
- University of California, San Diego