Slator, Paddy J., Cairo, Christopher W. and Burroughs, Nigel John (2015) Detection of diffusion heterogeneity in single particle tracking trajectories using a hidden Markov model with measurement noise propagation. PLoS One, 10 (10). e0140759. doi:10.1371/journal.pone.0140759 ISSN 1932-6203.

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Abstract

We develop a Bayesian analysis framework to detect heterogeneity in the diffusive behaviour of single particle trajectories on cells, implementing model selection to classify trajectories as either consistent with Brownian motion or with a two-state (diffusion coefficient) switching model. The incorporation of localisation accuracy is essential, as otherwise false detection of switching within a trajectory was observed and diffusion coefficient estimates were inflated. Since our analysis is on a single trajectory basis, we are able to examine heterogeneity between trajectories in a quantitative manner. Applying our method to the lymphocyte function-associated antigen 1 (LFA-1) receptor tagged with latex beads (4 s trajectories at 1000 frames s−1), both intra- and inter-trajectory heterogeneity were detected; 12–26% of trajectories display clear switching between diffusive states dependent on condition, whilst the inter-trajectory variability is highly structured with the diffusion coefficients being related by D1 = 0.68D0 − 1.5 × 104 nm2 s−1, suggestive that on these time scales we are detecting switching due to a single process. Further, the inter-trajectory variability of the diffusion coefficient estimates (1.6 × 102 − 2.6 × 105 nm2 s−1) is very much larger than the measurement uncertainty within trajectories, suggesting that LFA-1 aggregation and cytoskeletal interactions are significantly affecting mobility, whilst the timescales of these processes are distinctly different giving rise to inter- and intra-trajectory variability. There is also an ‘immobile’ state (defined as D < 3.0 × 103 nm2 s−1) that is rarely involved in switching, immobility occurring with the highest frequency (47%) under T cell activation (phorbol-12-myristate-13-acetate (PMA) treatment) with enhanced cytoskeletal attachment (calpain inhibition). Such ‘immobile’ states frequently display slow linear drift, potentially reflecting binding to a dynamic actin cortex. Our methods allow significantly more information to be extracted from individual trajectories (ultimately limited by time resolution and time-series length), and allow statistical comparisons between trajectories thereby quantifying inter-trajectory heterogeneity. Such methods will be highly informative for the construction and fitting of molecule mobility models within membranes incorporating aggregation, binding to the cytoskeleton, or traversing membrane microdomains.

Item Type:	Journal Article
Subjects:	Q Science > QC Physics
Divisions:	Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Library of Congress Subject Headings (LCSH):	Particle tracks (Nuclear physics), Brownian motion processes, Fluorescence microscopy, Nanoscience, Biophysics
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	16 October 2015
Dates:	Date Event 16 October 2015 Published 30 September 2015 Accepted 6 July 2015 Submitted
Volume:	10
Number:	10
Article Number:	e0140759
DOI:	10.1371/journal.pone.0140759
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	27 January 2016
Date of first compliant Open Access:	12 February 2016
Funder:	University of Warwick, Natural Sciences and Engineering Research Council of Canada (NSERC)
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