[Paper Review] Correlated random walks of human embryonic stem cell in-vitro

Laura E. Wadkin, Sirio Orozco-Fuentes+6 more|arXiv (Cornell University)|Feb 27, 2018

Microfluidic and Bio-sensing Technologies40 references3 citations

TL;DR

This study analyzes the correlated random walk dynamics of human embryonic stem cells (hESCs) in 2D culture using time-lapse imaging, revealing that isolated hESCs exhibit persistent, locally anisotropic motion aligned with their elongation axis over ~50-minute timescales. When in close proximity (<70 μm), cells synchronize directionality with a correlation length of ~25 μm, suggesting physical pseudopodial connections drive coordinated migration, which informs agent-based modeling of clonal colony formation.

ABSTRACT

We perform a detailed analysis of the migratory motion of human embryonic stem cells in two-dimensions, both when isolated and in close proximity to another cell, recorded with time-lapse microscopic imaging. We show that isolated cells tend to perform an unusual locally anisotropic walk, moving backwards and forwards along a preferred local direction correlated over a timescale of around 50 minutes and aligned with the axis of the cell elongation. Increasing elongation of the cell shape is associated with increased instantaneous migration speed. We also show that two cells in close proximity tend to move in the same direction, with the average separation of 70 um or less and the correlation length of around 25 um, a typical cell diameter. These results can be used as a basis for the mathematical modelling of the formation of clonal hESC colonies.

Motivation & Objective

• To characterize the migratory kinematics of single and paired hESCs in 2D culture.
• To determine how cell shape and proximity influence migration persistence and coordination.
• To quantify directional correlations between neighboring hESCs and identify optimal separation for coordinated motion.
• To provide empirical data for agent-based modeling of hESC clonal expansion in feeder-free systems.
• To explore the role of cell-cell interactions in early colony formation and survival.

Proposed method

• Time-lapse microscopy was used to track individual and paired hESCs over 7+ hours in 2D culture.
• Cell trajectories were analyzed using correlation functions to quantify directional persistence and inter-cell coordination.
• The pair correlation function C(r) was computed by projecting velocity vectors onto the inter-cell vector at each time step.
• A normalized correlation measure |C(r)| was used to assess average coordination strength, with comparison to uncorrelated integrated random walks (IRW).
• Cell shape and elongation were quantified to correlate morphology with instantaneous migration speed.
• Statistical analysis of velocity angles (θ), correlation (C(r)), and absolute correlation (|C(r)|) was performed across 50 cell pairs.

Experimental results

Research questions

• RQ1 How do isolated hESCs perform correlated random walks in 2D culture, and what is the timescale of directional persistence?
• RQ2 What is the optimal separation distance between hESCs for coordinated migration, and how does it relate to cell-cell proximity?
• RQ3 What is the correlation length of directional motion between neighboring hESCs, and what morphological features influence it?
• RQ4 How do pseudopodial connections between cells affect their collective migration behavior?
• RQ5 To what extent does cell shape elongation correlate with increased migration speed in isolated hESCs?

Key findings

• Isolated hESCs perform locally anisotropic correlated random walks with directional persistence over ~50 minutes, aligned with their cell elongation axis.
• Increased cell elongation is significantly correlated with higher instantaneous migration speed.
• hESCs in close proximity (<70 μm) exhibit strong directional coordination, with a correlation length of approximately 25 μm, matching a typical cell diameter.
• The average separation for maximal coordination is ~70 μm, beyond which motion becomes uncorrelated despite physical connections.
• At separations <70 μm, cells are often physically connected via pseudopodia, which likely facilitates synchronized movement.
• The absolute correlation |C(r)| for paired cells is consistent with that of an uncorrelated integrated random walk (2/π), indicating no net directional bias, but significant local coordination.