{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:48:34Z","timestamp":1782838114957,"version":"3.54.5"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 EY030413"],"award-info":[{"award-number":["P30 EY030413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY030190"],"award-info":[{"award-number":["R01 EY030190"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"International Foundation for Ethical Research (IFER)","award":["P30 EY030413"],"award-info":[{"award-number":["P30 EY030413"]}]},{"name":"International Foundation for Ethical Research (IFER)","award":["R01 EY030190"],"award-info":[{"award-number":["R01 EY030190"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["P30 EY030413"],"award-info":[{"award-number":["P30 EY030413"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["R01 EY030190"],"award-info":[{"award-number":["R01 EY030190"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Corneal fibroblasts are central to normal and abnormal wound healing in the cornea. During the wound healing process, several biochemical and biophysical signals that are present in the extracellular matrix (ECM) play critical roles in regulating corneal fibroblast behavior. The translocation and activation of Yes-associated protein (YAP)\u2014a main transcriptional factor in the Hippo signaling pathway\u2014is one example of mechanotransduction involving these signals. However, how corneal fibroblasts integrate these simultaneous cues is unknown. In this study, we utilized well-defined micropatterns of aligned collagen fibrils and other ECM proteins to explore the effects of cell density, topography, geometric confinement, and ECM composition on the translocation of YAP in corneal fibroblasts. We observed that when human corneal fibroblasts (HTKs) were confined to narrow micropatterns (50 \u03bcm and 100 \u03bcm) of proteins, there was a high degree of cell alignment irrespective of cell seeding density. However, the location of YAP was dependent upon the cell seeding density, ECM composition, and topography. YAP was more nuclear-localized on substrates coated with aligned collagen fibrils or fibronectin as compared to substrates coated with monomeric collagen, random collagen fibrils, or poly-L-Lysine. In addition, we also observed that YAP nuclear localization was significantly reduced when HTKs were cultured on aligned collagen fibrils, monomeric collagen, or fibronectin in the presence of monoclonal blocking antibodies against \u03b15 or \u03b21 integrin subunits. Finally, we observed that HTK cells formed fibrillar fibronectin on both monomeric collagen and aligned collagen fibrils. These findings provide new insights into how simultaneous biochemical and biophysical cues affect YAP localization in corneal fibroblasts.<\/jats:p>","DOI":"10.3390\/ijms26031183","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T04:01:39Z","timestamp":1738209699000},"page":"1183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts"],"prefix":"10.3390","volume":"26","author":[{"given":"Divya","family":"Subramanian","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-6498","authenticated-orcid":false,"given":"Nathaniel S.","family":"Tjahjono","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satweka","family":"Nammi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Miron-Mendoza","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor D.","family":"Varner","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA"},{"name":"Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0795-4539","authenticated-orcid":false,"given":"W. Matthew","family":"Petroll","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-318X","authenticated-orcid":false,"given":"David W.","family":"Schmidtke","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA"},{"name":"Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1167\/iovs.10-5657","article-title":"Three-Dimensional Analysis of Collagen Lamellae in the Anterior Stroma of the Human Cornea Visualized by Second Harmonic Generation Imaging Microscopy","volume":"52","author":"Morishige","year":"2011","journal-title":"Investig. 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