Issue 2, 2019

Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

Abstract

Collagen I is the primary extracellular matrix component of most solid tumors and influences metastatic progression. Collagen matrix engineering techniques are useful for understanding how this complex biomaterial regulates cancer cell behavior and for improving in vitro cancer models. Here, we establish an approach to tune collagen fibril architecture using PEG as an inert molecular crowding agent during gelation and cell embedding. We find that crowding produces matrices with tighter fibril networks that are less susceptible to proteinase mediated degradation, but does not significantly alter matrix stiffness. The resulting matrices have the effect of preventing cell spreading, confining cells, and reducing cell contractility. Matrix degradability and fibril length are identified as strong predictors of cell confinement. Further, the degree of confinement predicts whether breast cancer cells will ultimately undergo individual or collective behaviors. Highly confined breast cancer cells undergo morphogenesis to form either invasive networks reminiscent of aggressive tumors or gland and lobule structures reminiscent of normal breast epithelia. This morphological transition is accompanied by expression of cell–cell adhesion genes, including PECAM1 and ICAM1. Our study suggests that cell confinement, mediated by matrix architecture, is a design feature that tunes the transcriptional and morphogenic state of breast cancer cells.

Graphical abstract: Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

Supplementary files

Article information

Article type
Paper
Submitted
25 ก.ย. 2561
Accepted
21 พ.ย. 2561
First published
05 ธ.ค. 2561

Biomater. Sci., 2019,7, 618-633

Author version available

Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

S. K. Ranamukhaarachchi, R. N. Modi, A. Han, D. O. Velez, A. Kumar, A. J. Engler and S. I. Fraley, Biomater. Sci., 2019, 7, 618 DOI: 10.1039/C8BM01188E

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

Spotlight

Advertisements