Motion of chromosomal loci and the mean-squared displacement of a fractional Brownian motion in the presence of static and dynamic errors

Abstract

Mean-squared displacement (MSD) analysis is one of the most prevalent tools employed in the application of single-particle tracking to biological systems. In camera-based tracking, the effects of “static error” due to photon fluctuations and “dynamic error” due to motion blur on the MSD have been well-characterized for the case of pure Brownian motion, producing a known constant offset to the straight-line MSD. However, particles tracked in cellular environments often do not undergo pure Brownian motion, but instead can for instance exhibit anomalous diffusion wherein the MSD curve obeys a power law with respect to time, MSD=2D*τα, where D* is an effective diffusion coefficient and 0 < α ≤ 1. There are a number of models that can explain anomalous diffusive behavior in different subcellular contexts. Of these models, fractional Brownian motion (FBM) has been shown to accurately describe the motion of labeled particles such as mRNA and chromosomal loci as they traverse the cytoplasm or nucleoplasm (i.e. crowded viscoelastic environments). Despite the importance of FBM in biological tracking, there has yet to be a complete treatment of the MSD in the presence of static and dynamic errors analogous to the special case of pure Brownian motion. We here present a closed-form, analytical expression of the FBM MSD in the presence of both types of error. We have previously demonstrated its value in live-cell data by applying it to the study of chromosomal locus motion in budding yeast cells. Here we focus on validations in simulated data.