title: Spatio-Temporal Regulation of Rac1 Mobility by Actin Islands.
abstract: Rho GTPases play important roles in many aspects of cell migration, including polarity establishment and organizing actin cytoskeleton. In particular, the Rho GTPase Rac1 has been associated with the generation of protrusions at leading edge of migrating cells. Previously we showed the mobility of Rac1 molecules is not uniform throughout a migrating cell (Hinde E et. al. PNAS 2013). Specifically, the closer a Rac1 molecule is to the leading edge, the slower the molecule diffuses. Because actin-bound Rac1 diffuses slower than unbound Rac1, we hypothesized that regions of high actin concentration, called "actin islands", act as diffusive traps and are responsible for the non-uniform diffusion observed in vivo. Here, in silico model simulations demonstrate that equally spaced actin islands can regulate the time scale for Rac1 diffusion in a manner consistent with data from live-cell imaging experiments. Additionally, we find this mechanism is robust; different patterns of Rac1 mobility can be achieved by changing the actin islands' positions or their affinity for Rac1.
authors.affiliation: Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Molecular and Cellular Biophysics Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Vinal V
authors.initials: VV
authors.lastname: Lakhani
authors.affiliation: Australian Centre for NanoMedicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hinde
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
authors.affiliation: Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Molecular and Cellular Biophysics Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Elston
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000465:Algorithms; D015374:Biosensing Techniques; D003198:Computer Simulation; D042541:Intracellular Space / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D021381:Protein Transport; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D020830:rac1 GTP-Binding Protein