Endothelial cell stiffness and type drive the formation of biomechanically induced transcellular pores
Year: 2025
Type: article
Abstract: Formation of transcellular pores facilitates the transport of materials across endothelial barriers. In Schlemm’s canal (SC) endothelium, impaired pore formation is associated with glaucoma. However, our understanding of the cellular processes responsible for pore formation is limited by lack of in vitro assays. Here, we present a novel platform for studying transcellular pore formation in human endothelial cells. We induced pores in SC cells by seeding them atop micron-sized magnetic beads followed by application of a magnetic field to subject cells to a basal to apical force, mimicking in vivo biomechanical forces. The pore formation process was dynamic, with pores opening and closing. Glaucomatous cells exhibited impaired pore formation that correlated with their increased stiffness. We further discovered that application of forces from the apical to basal direction did not induce pores in SC cells but resulted in formation of pores in other types of endothelial cells. Our studies reveal the central role of cell mechanics in formation of transcellular pores in endothelial cells, and provide a new approach for investigating their associated underlying mechanism/s.
Source: Cell Reports
Authors: Seyed Mohammad Siadat, Haiyan Li, Brigid Millette, Babak N. Safa, Cydney A. Wong, M. Reza Bahrani Fard, Sietse T. Braakman, Ian Tay, Jacques A. Bertrand, A. Thomas Read, Lisa Schildmeyer, Kristin M. Perkumas, W. Daniel Stamer, Darryl R. Overby, C. Ross Ethier
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Investigating the Optic Nerve Head Remodeling in Glaucomatous Optic Neuropathy, G3952387132, The role of iris biomechanics and sex differences in primary angle-closure glaucoma, Microenvironmental regulation of barrier function in Schlemm's canal endothelial cells, Schlemm’s canal on a chip: A platform for screening a novel class of glaucoma medications, OCT Measurement of Trabecular Meshwork Function In Vivo, Selective Targeting of Schlemm's Canal Inner Wall for Next-Generation Glaucoma Drugs: Subpart A, G9000082343, G9000199325, T32 CTEng (Cellular and Tissue Engineering) Training Program, The role of iris biomechanics and sex differences in primary angle-closure glaucoma
OpenAlex ID: W4417523851