A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.
Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.
Gazzola
Mattia
M
Chair of Computational Science, ETH Zurich, Zurich, Switzerland.
Burckhardt
Christoph J
CJ
Bayati
Basil
B
Engelke
Martin
M
Greber
Urs F
UF
Koumoutsakos
Petros
P
D000260:Adenoviruses, Human / Q000502:physiology*; D001693:Biological Transport, Active / Q000502:physiology; D003198:Computer Simulation; D003593:Cytoplasm / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D020409:Molecular Motor Proteins / Q000502:physiology*; D013269:Stochastic Processes; D053586:Virus Internalization
D020409:Molecular Motor Proteins