Research Abstract:
Our research efforts are focused on understanding actin dynamics using a combination of analytic theory and computer simulation. Actin at cell edges polymerizes rapidly in response to external signals, and also displays an autonomous dynamic behavior in the cytoplasm. Several of the key molecular-level processes underlying actin dynamics are known, and these include polymerization/depolymerization of filaments, branching/debranching, capping/uncapping of filament ends, and bundling of filaments The goal of our work is to explore the types of dynamic actin structures that result from these processes, with the eventual hope of predicting the dependence of these structures on the type of external stimulus. In our simulations, we retain the coordinates of all actin subunits in filaments over time, thus obtaining a detailed picture of the three-dimensional structures that form, such as branched networks and bundles. These simulations have enabled us to make predictions regarding the force-velocity relation for objects propelled by actin polymerization, which have been tested by experiments on small beads. The simulations have also shown that actin filaments attached to an obstacle can provide efficient propulsion. Our studies of the dynamic structures formed during actin polymerization have shown that branched structures can form only in the early stages of polymerization. Recently, we have shown the hydrolyis of actin-bound ATP to ADP has profound effects on both force generation on force generation and polymerization dynamics. It can reduce the stall force of actin filament ensembles by up to a factor of three, and also lead to complex nonmonotonic dynamics in the polymerization of actin in vitro. At present, we are attempting to understand the origins of wave-like behavior and patches in intracellular actin.
Selected Publications:
Brooks FJ and Carlsson AE. Actin polymerization overshoots and hydrolysis as assayed by pyrene fluorescence. Biophys J 2008 95:1050-1062.
Carlsson AE. Model of reduction of polymerization forces by ATP Hydrolysis. Phys Biol 2008 8:035002:1-9.
Carlsson AE. Stimulation of actin polymerization by filament severing. Biophys J 2006 90:413-422.
Yang L, Sept D, Carlsson AE. Energetics and dynamics of constrainted actin filament bundling. Biophys J 2006 90:4295-4304.
Carlsson AE, Wear MA, Cooper JA. End vs. side branching by Arp2/3 Complex. Biophys J 2004 86:1074-1081.
Last Updated: 08/17/2009 |