In vivo, geometric cues from the extra-cellular matrix (ECM) are critical for the regulation of cell shape, adhesion and migration. During contact guidance, the fibrillar architecture of the ECM promotes an elongated cell shape and migration along the fibrils. The subcellular mechanisms by which cells sense ECM geometry and translate it into changes in shape and migration direction, are not understood. Here, we pattern linear fibronectin features to mimic fibrillar ECM and elucidate the mechanisms of contact guidance. By systematically varying patterned line spacing, we show that a 2 μm spacing is sufficient to promote cell shape elongation and migration parallel to the ECM, or contact guidance. As line spacing is increased, contact guidance increases without affecting migration speed. To elucidate the sub cellular mechanisms of contact guidance we quantitatively analyze protrusion dynamics and find that the structured ECM orients cellular protrusions parallel to the ECM. This spatial organization of protrusion relies on myosin II contractility and feedback between adhesion and Rac-mediated protrusive activity and we find that Arp2/3 inhibition can promote contact guidance. Together our data supports a model for contact guidance where the ECM enforces spatial constraints on the lamellipodia, that result in cell shape elongation and enforce migration direction.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 May 2017.
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#17,037,174
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Outputs of similar age from Molecular Biology of the Cell
#38
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