CompBio: Modeling cell shape changes using level set methods

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Many cellular processes require that cells change shape dynamically. For example, cells of the immune system respond to pathogenic invasions by crawling which involves cycles of extensions and contractions that deform their entire cell surface followed by phagocytosis, in which cells deform themselves around the captured invaders. Similarly, during cytokinesis, the last stage of cell division, cells rearrange themselves completely so as to produce two identical daughter cells. These cell shape changes are induced by the spatial and temporal regulation of a large number of cytoskeletal proteins. This regulation leads to spatial heterogeneity in the mechanical properties of the cell. A thorough understanding of how these processes are regulated requires both knowledge of the biochemical and genetic regulation of the cytoskeletal proteins, as well as an appreciation of the mechanical properties of the cytoskeleton. The complexity of the underlying system requires that conceptual models be tested by means of computational modeling coupled to quantitative measurements. However, because of the difficulty of modeling free boundaries inherent in cellular shape changes, traditional computational methods are not well suited. In this research we propose to provide a suitable framework, based on the level set formalism, for studying the interplay between the biochemical regulation of cytoskeletal proteins and the corresponding cellular deformations. Specifically: 1. Using the level set framework for describing moving and deformable boundaries, we will develop physical models of the mechanical properties of cells. These models will incorporate experimental data, from a wide range of Dictyostelium strains, describing the viscoelastic properties of the cell cortex and membrane. 2. We will test our model by simulating the cellular deformation induced by forces acting on the cell. Using a motorized micropipette aspirator, we will apply forces to Dictyostelium cells and measure the resultant deformation. These will then be compared to model predictions. These aims are designed to lead to a simple, yet accurate, mathematical representation of cellular deformation. By focusing on one of the principle processes of life, how cells deform in response to their mechanical environment, the proposed research will be of great scientific interest. More importantly, we expect our proposed research to have broader impact than the specific research proposed here. Our modeling framework will provide needed computational infrastructure that should prove useful for describing other biological responses, such as cell migration, in which differential localization of several proteins lead to cellular deformations. Additionally, by introducing graduate students to cutting edge interdisciplinary research, our proposed research will help develop the research leaders of the future.