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Bioengineering 2015, 2(3), 139-159; doi:10.3390/bioengineering2030139

Ovarian Cancer Cell Adhesion/Migration Dynamics on Micro-Structured Laminin Gradients Fabricated by Multiphoton Excited Photochemistry

1
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53717, USA
2
Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan
3
Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT 06030, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Gou-Jen Wang
Received: 11 April 2015 / Revised: 1 July 2015 / Accepted: 9 July 2015 / Published: 16 July 2015
(This article belongs to the Special Issue MEMS/NEMS Fabricated Tissue Scaffolding Devices)
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Abstract

Haptotaxis, i.e., cell migration in response to adhesive gradients, has been previously implicated in cancer metastasis. A better understanding of cell migration dynamics and their regulation could ultimately lead to new drug targets, especially for cancers with poor prognoses, such as ovarian cancer. Haptotaxis has not been well-studied due to the lack of biomimetic, biocompatible models, where, for example, microcontact printing and microfluidics approaches are primarily limited to 2D surfaces and cannot produce the 3D submicron features to which cells respond. Here we used multiphoton excited (MPE) phototochemistry to fabricate nano/microstructured gradients of laminin (LN) as 2.5D models of the ovarian basal lamina to study the haptotaxis dynamics of a series of ovarian cancer cells. Using these models, we found that increased LN concentration increased migration speed and also alignment of the overall cell morphology and their cytoskeleton along the linear axis of the gradients. Both these metrics were enhanced on LN compared to BSA gradients of the same design, demonstrating the importance of both topographic and ECM cues on the adhesion/migration dynamics. Using two different gradient designs, we addressed the question of the roles of local concentration and slope and found that the specific haptotactic response depends on the cell phenotype and not simply the gradient design. Moreover, small changes in concentration strongly affected the migration properties. This work is a necessary step in studying haptotaxis in more complete 3D models of the tumor microenvironment for ovarian and other cancers. View Full-Text
Keywords: ovarian cancer; ECM; haptotaxis; contact guidance; morphology; cytoskeleton ovarian cancer; ECM; haptotaxis; contact guidance; morphology; cytoskeleton
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

He, R.-Y.; Ajeti, V.; Chen, S.-J.; Brewer, M.A.; Campagnola, P.J. Ovarian Cancer Cell Adhesion/Migration Dynamics on Micro-Structured Laminin Gradients Fabricated by Multiphoton Excited Photochemistry. Bioengineering 2015, 2, 139-159.

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