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The mechanisms underlying directional growth toward the apex are not completely understood. Here, a microfluidic chip\u2010based approach is utilized to test whether calvarial osteoblast progenitors undergo haptotaxis on a gradient of Fibronectin1 (FN1) via lamellipodia. Mimicking the embryonic cranial mesenchyme's FN1 pattern, FN1 gradients is established in the chip using computer modeling and fluorescent labeling. Primary mouse calvarial osteoblast progenitors are plated in the chip along an array of segmented gradients of adsorbed FN1. The study performs single\u2010cell tracking and measures protrusive activity. Haptotaxis is observed at an intermediate FN1 concentration, with an average directional migration index (yFMI) of 0.07, showing a significant increase compared to the control average yFMI of \u20100.01. A significant increase in protrusive activity is observed during haptotaxis. Haptotaxis is an Arp2\/3\u2010dependent, lamellipodia\u2010mediated process. Calvarial osteoblast progenitors treated with the Arp2\/3 (Actin Related Protein 2\/3 complex) inhibitor CK666 show significantly diminished haptotaxis, with an average yFMI of 0.01. Together, these results demonstrate haptotaxis on an FN1 gradient as a new mechanism in the apical expansion of calvarial osteoblast progenitors during development and shed light on the etiology of calvarial defects.<\/jats:p>","DOI":"10.1002\/smll.202401717","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T12:56:22Z","timestamp":1726577782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lamellipodia\u2010Mediated Osteoblast Haptotaxis Guided by Fibronectin Ligand Concentrations on a Multiplex Chip"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3227-6813","authenticated-orcid":false,"given":"Chao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-5536","authenticated-orcid":false,"given":"Xiaotian","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biology Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seoyoung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biology Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2477-7917","authenticated-orcid":false,"given":"Melissa L.","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Biology Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-6552","authenticated-orcid":false,"given":"Radhika P.","family":"Atit","sequence":"additional","affiliation":[{"name":"Department of Biology Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-6845","authenticated-orcid":false,"given":"Samuel E.","family":"Senyo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.227"},{"key":"e_1_2_9_2_1","volume":"57","author":"Ferguson J. 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