title: Substrate-bound protein gradients to study haptotaxis.
abstract: Cells navigate in response to inhomogeneous distributions of extracellular guidance cues. The cellular and molecular mechanisms underlying migration in response to gradients of chemical cues have been investigated for over a century. Following the introduction of micropipettes and more recently microfluidics for gradient generation, much attention and effort was devoted to study cellular chemotaxis, which is defined as guidance by gradients of chemical cues in solution. Haptotaxis, directional migration in response to gradients of substrate-bound cues, has received comparatively less attention; however, it is increasingly clear that in vivo many physiologically relevant guidance proteins - including many secreted cues - are bound to cellular surfaces or incorporated into extracellular matrix and likely function via a haptotactic mechanism. Here, we review the history of haptotaxis. We examine the importance of the reference surface, the surface in contact with the cell that is not covered by the cue, which forms a gradient opposing the gradient of the protein cue and must be considered in experimental designs and interpretation of results. We review and compare microfluidics, contact printing, light patterning, and 3D fabrication to pattern substrate-bound protein gradients in vitro. The range of methods to create substrate-bound gradients discussed herein makes possible systematic analyses of haptotactic mechanisms. Furthermore, understanding the fundamental mechanisms underlying cell motility will inform bioengineering approaches to program cell navigation and recover lost function.
authors: McGill Program in Neuroengineering, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, QC , Canada ; Genome Quebec Innovation Centre, McGill University , Montréal, QC , Canada.
authors: Sébastien G
authors: SG
authors: Ricoult
authors: McGill Program in Neuroengineering, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, QC , Canada.
authors: Timothy E
authors: TE
authors: Kennedy
authors: McGill Program in Neuroengineering, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, QC , Canada ; Genome Quebec Innovation Centre, McGill University , Montréal, QC , Canada ; McGill Program in Neuroengineering, Department of Biomedical Engineering, McGill University , Montreal, QC , Canada.
authors: David
authors: D
authors: Juncker
keywords: digital gradient; haptotaxis; immobilized gradient; reference surface; substrate-bound gradient