小柯机器人

中山大学许杰研究小组探明了NINJ1调控机械应变下的质膜脆性。2025年6月9日出版的《自然》杂志发表了这项成果。

在这里，该研究团队构建了一个384孔的细胞拉伸系统，提供精确的，可复制的菌株培养细胞。使用该系统，该课题组筛选了10843个siRNA，靶向2726个多通跨膜蛋白，用于菌株诱导的膜通透性变化。该筛选结果发现，最近提出的一种调节焦亡和其他溶解性细胞死亡的蛋白NINJ1名列榜首。研究小组证明了NINJ1是机械应变诱导的质膜破裂（PMR）的关键调节因子，而不需要刺激任何细胞死亡程序。质膜上的NINJ1水平与使膜破裂所需的力呈负相关。在焦亡的情况下，NINJ1本身不足以使膜完全破裂，需要额外的机械力来实现完全的PMR。他们的研究表明，NINJ1是膜生物力学特性的真正决定因素。他们的研究还表明，不同机械微环境组织的PMR受到NINJ1表达和外力差异的微调。

研究人员表示，质膜的完整性几乎对细胞功能的所有方面都至关重要。机械力可以调节质膜损伤，但在机械应变下是否存在调节质膜完整性的大分子尚不清楚。

附：英文原文

Title: NINJ1 regulates plasma membrane fragility under mechanical strain

Author: Zhu, Yunfeng, Xiao, Fang, Wang, Yiling, Wang, Yufang, Li, Jialin, Zhong, Dongmei, Huang, Zhilei, Yu, Miao, Wang, Zhirong, Barbara, Joshua, Plunkett, Christopher, Zeng, Mengxue, Song, Yiyan, Tan, Tian, Zhang, Ruibin, Xu, Kezhen, Wang, Zhongxing, Cai, Changjie, Guan, Xiangdong, Hammack, Scott, Zhang, Liang, Shi, Zheng, Xiang, Fu-li, Shao, Feng, Xu, Jie

Issue&Volume: 2025-06-09

Abstract: Plasma membrane integrity is vital for nearly all aspects of cell functioning1. Mechanical forces can cause plasma membrane damage2, but it is not known whether there are large molecules that regulate plasma membrane integrity 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 siRNAs targeting 2,726 multi-pass transmembrane proteins for strain-induced membrane permeability changes. The screen identified NINJ1, a protein recently proposed to regulate pyroptosis and other lytic cell death3,4, as the top hit. We demonstrate that NINJ1 is a critical regulator for mechanical strain-induced plasma membrane rupture (PMR), without the need of stimulating any cell death programs. NINJ1 level on the plasma membrane is inversely correlated to 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 work 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.

DOI: 10.1038/s41586-025-09222-5

Source: https://www.nature.com/articles/s41586-025-09222-5

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html