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.

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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

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article

Endothelial cell stiffness and type drive the formation of biomechanically induced transcellular pores

Darryl R. Overby, Sietse T. Braakman, Haiyan Li, Lisa A. Schildmeyer et al.
Cell Reports
Glaucoma and retinal disorders
article

Endothelial cell stiffness and type drive the formation of biomechanically induced transcellular pores

Darryl R. Overby, Sietse T. Braakman, Haiyan Li, Lisa A. Schildmeyer, Mohammad Reza Bahrani Fard, Cydney A. Wong, Babak N. Safa, W. Daniel Stamer, Ignacius Y. Y. Tay, A. Thomas Read, Seyed Mohammad Siadat, Jacques Bertrand, Kristin Perkumas, Brigid A. Millette
article en

Abstract

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.

Cell ReportsVol. 45(1)
Georgia Institute of Technology (US), Duke University (US), The Wallace H. Coulter Department of Biomedical Engineering (US), Imperial College London (GB)
BrightFocus Foundation, Georgia Research Alliance, National Institutes of Health, Biotechnology and Biological Sciences Research Council
Openalex Percentile: Top 44%
Glaucoma and retinal disorders
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