Jump to main content
Jump to site search

Issue 21, 2019

Integrating nanofibers with biochemical gradients to investigate physiologically-relevant fibroblast chemotaxis

Author affiliations

Abstract

Persistent cell migration can occur due to anisotropy in the extracellular matrix (ECM), the gradient of a chemo-effector, or a combination of both. Through a variety of in vitro platforms, the contributions of either stimulus have been extensively studied, while the combined effect of both cues remains poorly described. Here, we report an integrative microfluidic chemotaxis assay device that enables the study of single cell chemotaxis on ECM-mimicking, aligned, and suspended nanofibers. Using this assay, we evaluated the effect of fiber spacing on the morphology and chemotaxis response of embryonic murine NIH/3T3 fibroblasts in the presence of temporally invariant, linear gradients of platelet-derived growth factor-BB (PDGF-BB). We found that the strength of PDGF-mediated chemotaxis response depends on not only the gradient slope but also the cell morphology. Low aspect ratio (3.4 ± 0.2) cells on flat substrata exhibited a chemotaxis response only at a PDGF-BB gradient of 0–10 ng mL−1. However, high aspect ratio (19.1 ± 0.7) spindle-shaped cells attached to individual fibers exhibited maximal chemotaxis response at a ten-fold shallower gradient of 0–1 ng mL−1, which was robustly maintained up to 0–10 ng mL−1. Quadrilateral-shaped cells of intermediate aspect ratio (13.6 ± 0.8) attached to two fibers exhibited a weaker response compared to the spindle-shaped cells, but still stronger compared to cells attached to 2D featureless substrata. Through pharmacological inhibition, we show that the mesenchymal chemotaxis pathway is conserved in cells on fibers. Altogether, our findings show that chemotaxis on ECM-mimicking fibers is modulated by fiber spacing-driven cell shape and can be significantly different from the behavior observed on flat 2D substrata. We envisage that this microfluidic platform will have wide applicability in understanding the combined role of ECM architecture and chemotaxis in physiological and pathological processes.

Graphical abstract: Integrating nanofibers with biochemical gradients to investigate physiologically-relevant fibroblast chemotaxis

Supplementary files

Article information


Submitted
21 Jun 2019
Accepted
02 Sep 2019
First published
02 Sep 2019

Lab Chip, 2019,19, 3641-3651
Article type
Paper
Author version available

Integrating nanofibers with biochemical gradients to investigate physiologically-relevant fibroblast chemotaxis

C. M. Morrow, A. Mukherjee, M. A. Traore, E. J. Leaman, A. Kim, E. M. Smith, A. S. Nain and B. Behkam, Lab Chip, 2019, 19, 3641 DOI: 10.1039/C9LC00602H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.


Social activity

Search articles by author

Spotlight

Advertisements