A hidden Markov model for single particle tracks quantifies dynamic interactions between LFA-1 and the actin cytoskeleton.
The extraction of hidden information from complex trajectories is a continuing problem in single-particle and single-molecule experiments. Particle trajectories are the result of multiple phenomena, and new methods for revealing changes in molecular processes are needed. We have developed a practical technique that is capable of identifying multiple states of diffusion within experimental trajectories. We model single particle tracks for a membrane-associated protein interacting with a homogeneously distributed binding partner and show that, with certain simplifying assumptions, particle trajectories can be regarded as the outcome of a two-state hidden Markov model. Using simulated trajectories, we demonstrate that this model can be used to identify the key biophysical parameters for such a system, namely the diffusion coefficients of the underlying states, and the rates of transition between them. We use a stochastic optimization scheme to compute maximum likelihood estimates of these parameters. We have applied this analysis to single-particle trajectories of the integrin receptor lymphocyte function-associated antigen-1 (LFA-1) on live T cells. Our analysis reveals that the diffusion of LFA-1 is indeed approximately two-state, and is characterized by large changes in cytoskeletal interactions upon cellular activation.
Das
Raibatak
R
Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, Vancouver, British Columbia, Canada. dodo@math.ubc.ca
Cairo
Christopher W
CW
Coombs
Daniel
D
D000199:Actins / Q000378:metabolism*; D003198:Computer Simulation; D003599:Cytoskeleton / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008390:Markov Chains; D008954:Models, Biological; D015233:Models, Statistical; D009038:Motion; D025941:Protein Interaction Mapping / Q000379:methods*; D013601:T-Lymphocytes / Q000378:metabolism*
D000199:Actins; D016169:Lymphocyte Function-Associated Antigen-1