Endothelial cell stiffness and type drive the formation of biomechanically induced transcellular pores
Formation of transcellular pores facilitates material transport across endothelial barriers. In Schlemm's canal (SC) endothelium, impaired pore formation is linked to glaucoma, but the underlying processes remain poorly understood due to a lack of in vitro assays. Here, we present a platform to study pore formation in human endothelial cells. Pores were induced in SC cells by seeding them atop micron-sized magnetic beads and applying a magnetic field to generate basal-to-apical forces, mimicking in vivo biomechanics. Pore formation was dynamic, with pores opening and closing. Glaucomatous cells showed impaired pore formation, which correlated with increased stiffness. Notably, apical-to-basal forces failed to induce pores in SC cells but triggered pore formation in other endothelial types. These findings highlight the central role of cell mechanics in transcellular pore formation and provide an approach to investigate the mechanisms underlying this process.
Authors
- Darryl R. Overby (ORCID: https://orcid.org/0000-0001-9894-7515)
- Sietse T. Braakman (ORCID: https://orcid.org/0000-0003-2089-1595)
- Haiyan Li (ORCID: https://orcid.org/0000-0002-3856-9767)
- Lisa A. Schildmeyer
- Mohammad Reza Bahrani Fard
- Cydney A. Wong (ORCID: https://orcid.org/0000-0001-9381-5847)
- Babak N. Safa (ORCID: https://orcid.org/0000-0002-1849-2870)
- W. Daniel Stamer (ORCID: https://orcid.org/0000-0002-2504-8997)
- Ignacius Y. Y. Tay (ORCID: https://orcid.org/0000-0002-1597-6351)
- A. Thomas Read (ORCID: https://orcid.org/0000-0002-2764-6413)
- Seyed Mohammad Siadat (ORCID: https://orcid.org/0000-0002-5063-0305)
- Jacques Bertrand
- Kristin Perkumas
- Brigid A. Millette
Institutions
- Georgia Institute of Technology (US)
- Duke University (US)
- The Wallace H. Coulter Department of Biomedical Engineering (US)
- Imperial College London (GB)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1016/j.celrep.2025.116668
- Primary Topic
- Glaucoma and retinal disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- BrightFocus Foundation
- Georgia Research Alliance
- National Institutes of Health
- Biotechnology and Biological Sciences Research Council