Cells choose the path less potholed

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Science Translational Medicine  19 Aug 2015:
Vol. 7, Issue 301, pp. 301ec144
DOI: 10.1126/scitranslmed.aad0232

How do adherent cells decide where to go? It is known that the microenvironment provides guidance cues through molecular gradients, fields, forces, and flows. Now, Jeon et al. show that tiny potholes can also affect cell migration, analogous to how people (and their vehicles) avoid rough patches of road.

Fibroblasts were cultured on a smooth glass surface patterned with arrays of nanoscale potholes. When these potholes exceeded a critical depth of ~100 nm, cell protrusions could not reach the bottom to form stable focal adhesions. As a consequence, cells did not adhere strongly to regions with high pothole density. To better understand this behavior, the authors varied pothole spacing as a continuous gradient. This gradient resulted in spatially asymmetric focal adhesion formation, polarizing cells to migrate rapidly and directionally towards lower pothole densities. To negotiate high pothole densities and go “off-road,” cells were modified to overexpress Talin-1, to enhance focal adhesion formation. Talin-1 overexpressing cells were unaffected by the density gradient and randomly migrated across the pothole patterns.

Topographical nanopatterning of implantable materials could be used to direct cell migration and self-organization, complementing existing molecular and physical design strategies for biomaterials. Further studies are necessary to establish the generality of this mechanism for different cell types. An intriguing possibility is that pothole patterns on biomedical implants could diminish macrophage adhesion and delay the foreign body response in vivo.

H. Jeon et al., Directed cell migration and organization via nanocrater-patterned cell-repellent interfaces. Nat. Mat. 10.1038/nmat4342 (2015). [Full Text]

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