A platform for assessing chemotactic migration within a spatiotemporally defined 3D microenvironment

作者:Abhyankar Vinay V; Toepke Michael W; Cortesio Christa L; Lokuta Mary A; Huttenlocher Anna; Beebe David J*
来源:Lab on a Chip, 2008, 8(9): 1507-1515.
DOI:10.1039/b803533d

摘要

While the quantification of cell movement within defined biochemical gradients is now possible with microfluidic approaches, translating this capability to biologically relevant three-dimensional microenvironments remains a challenge. We introduce an accessible platform, requiring only standard tools (e.g. pipettes), that provides robust soluble factor control within a three-dimensional biological matrix. We demonstrate long-lasting linear and non-linear concentration profiles that were maintained for up to ten days using 34.5 mu L solute volume. We also demonstrate the ability to superimpose local soluble factor pulses onto existing gradients via defined dosing windows. The combination of long-term and transient gradient characteristics within a three-dimensional environment opens the door for signaling studies that investigate the migratory behavior of cells within a biologically representative matrix. To this end, we apply temporally evolving and long-lasting gradients to study the chemotactic responses of human neutrophils and the invasion of metastatic rat mammary adenocarcinoma cells (MtLN3) within three-dimensional collagen matrices.

  • 出版日期2008-9