Mechanics of Intracellular Pathogens and Biomimetic Systems Propelled by Actin Comet Tails

Brown University, Providence RI

Investigators

Abstract

Abstract A number of pathogenic bacteria responsible for diseases like listeriosis, meningitis and gas-troenteritis hijack the protein machinery of the infected cells to form a filamentous actin comet tail that propels them within these cells. A physical understanding of the forces that lead to this motion can provide a means to control spreading of infections and to design biomimetic systems with applications in drug delivery. The objective of this proposal is to develop quantitative models to predict how the filament-level properties determine the macroscale motion of bacteria and biomimetic cargo. The proposed work has two main themes. The first theme is to measure and analyze the motility of various actin-propelled biomimetic systems and to study how structural and mechanical properties of actin networks and the shape and size of biomimetic systems influence their trajectories. The second theme focuses on the development of a mechanics-based model for motility where the actin comet tail is assembled by stochastic and load dependent growth of actin filaments. If successful, the results of the proposed work will allow us to tailor the motion of biomimetic systems by varying the molecular properties of the actin networks such as the statistical distributions of the filament lengths and orientations, degree of cross-linking and kinetics of polymerization. Since actin-based networks are ubiquitously used to generate mechanical forces in cells, elucidation of the relationship between molecular structure and microscopic motion will also have important implications for understanding cell motility, wound healing, filopodial extensions and morphogenesis. The results from this project will be included in the courses on computational methods and experimental techniques the PIs have developed. The PIs will participate in the Research Experience for Teachers (RET) outreach program and provide middle and high school teachers with software modules and experimental data that they can use in their classes.