 NINJ1 regulates plasma membrane fragility under mechanical strainYunfeng Zhu,
Fang Xiao,
Yiling Wang,
Yufang Wang,
Jialin Li,
Dongmei Zhong,
Zhilei Huang,
Miao Yu,
Zhirong Wang,
Joshua Barbara,
Christopher Plunkett,
Mengxue Zeng,
Yiyan Song,
Tian Tan,
Ruibin Zhang,
Kezhen Xu,
Zhongxing Wang,
Changjie Cai,
Xiangdong Guan,
Scott Hammack,
Liang Zhang,
Zheng Shi (),
Fu-li Xiang (),
Feng Shao and
Jie Xu ()
Nature, 2025, vol. 644, issue 8078, 1088-1096 Abstract: Abstract The integrity of the plasma membrane is vital for nearly all aspects of cell functioning1. Mechanical forces can cause plasma membrane damage2, but it is unclear whether there are large molecules that regulate the integrity of the plasma membrane under mechanical strain. Here we constructed a 384-well cellular-stretch system that delivers precise, reproducible strain to cultured cells. Using the system, we screened 10,843 small interfering RNAs (siRNAs) targeting 2,726 multipass transmembrane proteins for strain-induced membrane permeability changes. The screen identified NINJ1—a protein that was recently proposed to regulate pyroptosis and other lytic cell death3,4—as the top hit. We demonstrate that NINJ1 is a critical regulator of mechanical-strain-induced plasma membrane rupture (PMR), without the need for stimulating any cell death programs. NINJ1 levels on the plasma membrane are inversely correlated with the amount of force required to rupture the membrane. In the pyroptosis context, NINJ1 on its own is not sufficient to fully rupture the membrane, and additional mechanical force is required for full PMR. Our study establishes that NINJ1 functions as a bona fide determinant of membrane biomechanical properties. Our study also suggests that PMR across tissues of distinct mechanical microenvironments is subjected to fine-tuning by differences in NINJ1 expression and external forces. Date: 2025 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:644:y:2025:i:8078:d:10.1038_s41586-025-09222-5 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-025-09222-5 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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