The First Passage Probability of Intracellular Particle Trafficking

TL;DR

This paper introduces the first passage probability (FPP) as a robust, assumption-free method to analyze intracellular particle movement, distinguishing various motion types from tracked data and assessing effects of molecular treatments.

Contribution

It presents FPP as a novel, data-reduction technique that characterizes complex intracellular particle trajectories without relying on smoothing or arbitrary thresholds.

Findings

FPP effectively differentiates diffusion, ballistic, and mixed motions.

FPP quantifies effects of molecular treatments on particle trafficking.

Method applied successfully to endocytic vesicle data.

Abstract

The first passage probability (FPP), of trafficked intracellular particles reaching a displacement L, in a given time t or inverse velocity S = t/L, can be calculated robustly from measured particle tracks, and gives a measure of particle movement in which different types of motion, e.g. diffusion, ballistic motion, and transient run-rest motion, can readily be distinguished in a single graph, and compared with mathematical models. The FPP is attractive in that it offers a means of reducing the data in the measured tracks, without making assumptions about the mechanism of motion: for example, it does not employ smoothing, segementation or arbitrary thresholds to discriminate between different types of motion in a particle track. Taking experimental data from tracked endocytic vesicles, and calculating the FPP, we see how three molecular treatments affect the trafficking. We show the FPP can quantify complicated movement which is neither completely random nor completely deterministic, making it highly applicable to trafficked particles in cell biology.