Ranking migration cue contributions to guiding individual fibroblasts faced with a directional decision in simple microfluidic bifurcations

Quang Long Pham, Anh Tong, Lydia N. Rodrigues, Yang Zhao, Migle Surblyte, Diomar Ramos, John Brito, Adwik Rahematpura, Roman S. Voronov

Research output: Contribution to journalArticle

Abstract

Directed cell migration in complex micro-environments, such as in vivo pores, is important for predicting locations of artificial tissue growth and optimizing scaffold architectures. Yet, the directional decisions of cells facing multiple physiochemical cues have not been characterized. Hence, we aim to provide a ranking of the relative importance of the following cues to the decision-making of individual fibroblast cells: chemoattractant concentration gradient, channel width, mitosis, and contact-guidance. In this study, bifurcated micro-channels with branches of different widths were created. Fibroblasts were then allowed to travel across these geometries by following a gradient of platelet-derived growth factor-BB (PDGF-BB) established inside the channels. Subsequently, a combination of statistical analysis and image-based diffusion modeling was used to report how the presence of multiple complex migration cues, including cell-cell influences, affect the fibroblast decision-making. It was found that the cells prefer wider channels over a higher chemoattractant gradient when choosing between asymmetric bifurcated branches. Only when the branches were symmetric in width did the gradient become predominant in directing which path the cell will take. Furthermore, when both the gradient and the channels were symmetric, contact guidance became important for guiding the cells in making directional choices. Based on these results we were able to rank these directional cues from most influential to the least as follows: mitosis > channel width asymmetry > chemoattractant gradient difference > and contact-guidance. It is expected that these results will benefit the fields of regenerative medicine, wound healing and developmental biology.

Original languageEnglish (US)
Pages (from-to)208-220
Number of pages13
JournalIntegrative biology : quantitative biosciences from nano to macro
Volume11
Issue number5
DOIs
StatePublished - May 1 2019

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

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