First-passage-probability analysis of active transport in live cells.

The first-passage-probability can be used as an unbiased method for determining the phases of motion of individual organelles within live cells. Using high speed microscopy, we observe individual lipid droplet tracks and analyze the motor protein driven motion. At short passage lengths (< 10-2µm), a log-normal distribution in the first-passage-probability as a function of time is observed, which switches to a Gaussian distribution at longer passages due to the running motion of the motor proteins. The mean first-passage times ((tFPT)) AS a function of the passage length (L), averaged over a number of runs for a single lipid droplet, follow a power law distribution (tFPT)~Lα, α > 2, at short times due to a passive subdiffusive process. This changes to another power law at long times where 1 < α < 2 corresponding to sub-ballistic superdiffusive motion, an active process. Subdiffusive passive mean square displacements are observed as a function of time, (r²) ~ tβ, where 0 < β < 1 at short times again crossing over to an active sub-ballistic superdiffusive result 1 < β < 2 at longer times. Consecutive runs of the lipid droplets add additional independent Gaussian peaks to a cumulative first-passage-probability distribution indicating that the speeds of sequential phases of motion are independent and biochemically well regulated. As a result we propose a model for motor driven lipid droplets that exhibits a sequential run behavior with occasional pauses. [ABSTRACT FROM AUTHOR]