Campus Units

Chemical and Biological Engineering, Genetics, Development and Cell Biology, Electrical and Computer Engineering

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Accepted Manuscript

Publication Date

9-2018

Journal or Book Title

Biomedical Microdevices

Volume

20

First Page

62

DOI

10.1007/s10544-018-0309-1

Abstract

Cells communicate through the extracellular matrix (ECM) in many physiological and pathological processes. This is particularly important during cell migration, where cell communication can alter both the speed and the direction of migration. However, most cell culture systems operate with large volumes relative to cell numbers, creating low cell densities and diluting factors that mediate cell communication. Furthermore, they lack the ability to isolate single cells or small groups of cells. Droplet forming devices allow for an ability to embed single or small groups of cells into small volume segregated 3D environments, increasing the cell density to physiological levels. In this paper we show a microfluidic droplet device for fabricating 3D collagen-based microtissues to study breast cancer cell motility. MDA-MB-231 cells fail to spread and divide in small, thin chambers. Cell migration is also stunted as compared to thick 3D gels. However, larger chambers formed by a thicker devices promote cell spreading, cell division and faster migration. In the large devices, both cell-ECM and cell-cell interactions affect cell motility. Increasing collagen density decreases cell migration and increasing the number of cells per chamber increases cell migration speed. Furthermore, cells appear to sense both the ECM-chamber wall interface as well as other cells. Cells migrate towards the ECM-chamber interface if within roughly 150 μm, whereas cells further than 150 μm tend to move towards the center of the chamber. Finally, while cells do not show enhanced movement towards the center of mass of a cell cluster, their migration speed is more variable when further away from the cell cluster center of mass. These results show that microfluidic droplet devices can array 3D collagen gels and promote cell spreading, division and migration similar to what is seen in thick 3D collagen gels. Furthermore, they can provide a new avenue to study cell migration and cell-cell communication at physiologically relevant cell densities.

Comments

This is a post-peer-review, pre-copyedit version of an article published in Biomedical Microdevices. The final authenticated version is available online at: https://doi.org/10.1007/s10544-018-0309-1. Posted with permission.

Copyright Owner

Springer Science+Business Media, LLC

Language

en

File Format

application/pdf

Available for download on Tuesday, July 30, 2019

Published Version

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