Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells

Taisuke Kojima; Christopher Moraes; Stephen P Cavnar; Gary D Luker; Shuichi Takayama

doi:10.1016/j.actbio.2014.11.033

Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells

Acta Biomater. 2015 Feb:13:68-77. doi: 10.1016/j.actbio.2014.11.033. Epub 2014 Nov 24.

Authors

Taisuke Kojima¹, Christopher Moraes², Stephen P Cavnar², Gary D Luker³, Shuichi Takayama⁴

Affiliations

¹ Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
² Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
³ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA. Electronic address: gluker@med.umich.edu.
⁴ Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address: takayama@umich.edu.

Abstract

This paper describes a novel technique for fabricating spatially defined cell-laden collagen hydrogels, using patterned, non-adhesive polyacrylamide-coated polydimethylsiloxane (PDMS) surfaces as a template. Precisely patterned embedded co-cultures of breast cancer cells and chemokine-producing cells generated with this technique revealed matrix-dependent and chemokine isoform-dependent migration of cancer cells. CXCL12 chemokine-secreting cells induce significantly more chemotaxis of cancer cells when the 3-D extracellular matrix (ECM) includes components that bind the secreted CXCL12 chemokines. Experimental observations using cells that secrete CXCL12 isoforms with different matrix affinities together with computational simulations show that stronger ligand-matrix interactions sharpen chemoattractant gradients, leading to increased chemotaxis of the CXCL12 gradient-sensing CXCR4 receptor-expressing (CXCR4+) cells patterned in the hydrogel. These results extend our recent report on CXCL12 isoform-dependent chemotaxis studies from 2-D to 3-D environments and additionally reveal the important role of ECM composition. The developed technology is simple, versatile and robust; and as chemoattractant-matrix interactions are common, the methods described here should be broadly applicable for study of physiological migration of many different cell types in response to a variety of chemoattractants.

Keywords: Cell migration; Gradient; Hydrogels; Micropatterning; Surface modification.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement*
Chemokine CXCL12 / metabolism*
Extracellular Matrix / chemistry*
Female
Humans
Hydrogels / chemistry*
Neoplasm Proteins / metabolism*
Receptors, CXCR4 / metabolism

Substances

CXCL12 protein, human
CXCR4 protein, human
Chemokine CXCL12
Hydrogels
Neoplasm Proteins
Receptors, CXCR4

Abstract

Publication types

MeSH terms

Substances

Grants and funding