Overview Cell Structures Cell Migration Cell Division  

Substrate Dimensionality as a Guidance Cue for Cell Migration

Chang et al, Biophys. J. 104:313-321 (2013)

Since cell behavior is known to differ significantly in 1D, 2D, or 3D environments, we hypothesize that migrating cells are able to sense the dimension of the environment as a guidance cue.This possibility was investigated by culturing NIH 3T3 fibroblasts on micropatterned substrates where the path of migration alternates between 1D lines and 2D rectangles.

Preference of normal NIH 3T3 fibroblasts to stay in 2D regions.

A migrating cell turns around at a 2D-1D interface to stay in the 2D region, suggesting a preference for 2D regions. Over time an increasing percentage cells accumulate in 2D regions. Fluorescent beads shown in red in the movie allow identification of the adhesive, patterned area. Recording time, 10 hrs.

Lack of preference of blebbistatin-treated NIH 3T3 fibroblasts for 2D regions.

A cell treated with 10┬ÁM blebbistatin is able to migrate through a 2D region and exit into a 1D region, indicating that myosin II is required for dimension sensing. Corresponding traction force microscopy shows stronger mechanical output in 2D regions than along 1D lines, suggesting that differential myosin II dependent traction forces may determine the preferential localization. Recording time, 14 hrs.

Lack of preference of ras-transformed NIH 3T3 fibroblasts to stay in 2D regions.

A migrating H-ras transformed 3T3 (PAP2) cell enters and exits the 2D region, suggesting that at least some types of transformed cells are defective in dimension sensing. Recording time, 4 hours.

Weak directional persistence of ras-transformed NIH 3T3 fibroblasts on 2D regions.

A migrating H-ras transformed 3T3 (PAP2) cell turns around completely as it enters the 2D region and exits along the entry 1D line. The weak persistence may further contribute to the defect in dimension sensing. Recording time, 10 hrs.