title: Surface-templated hydrogel patterns prompt matrix-dependent migration of breast cancer cells towards chemokine-secreting cells.
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.
authors.affiliation: Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Moraes
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Cavnar
authors.affiliation: 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.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Luker
authors.affiliation: 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.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takayama
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D020100:Hydrogels; D009363:Neoplasm Proteins; D019718:Receptors, CXCR4
keywords: Cell migration; Gradient; Hydrogels; Micropatterning; Surface modification