ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Zheng Wang,Feng Xu,Di Wu,Wei Huang,Zhiqin Chu,Yuan Lin
Cells need to migrate through confined spaces during processes such as embryo development and cancer metastasis. However, the fundamental question of how confinement size and surrounding rigidity collectively regulate the migration capability of cells remains unclear. Here, by utilizing maskless photolithography with a digital micromirror device (DMD), a microchannel with precisely controlled width and wall stiffness (similar to those exhibited by natural tissues) is fabricated. We find that increasing the rigidity of the confining wall leads to a more reduced nuclear volume but has no detectable influence on the myosin expression level in the cells. More interestingly, a biphasic trend of the cell speed is observed, with the migration velocity reaching its minimum at an intermediate wall rigidity of ∼10 kPa. A motor-clutch-based pulling race model is then proposed, which suggests that such biphasic dependence is due to the fact that a very soft channel wall will result in small deformation of the nucleus and consequently reduced cell-wall friction, while larger myosin-based crawling force can be triggered by a stiff confining boundary, both leading to a relatively high migration speed. These findings could provide critical insights into novel strategies for controlling the movement of cells and the design of high-performance biological materials.
研究领域:
细胞生物学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Fang Zhou,Robert J Ju,Chenlu Kang,Jiayi Li,Ao Yang,Alexandre Libert,Yujie Sun,Ling Liang,Youwei Ai,Xiaoqing Hu,Samantha J Stehbens,Congying Wu
Cells in highly crowded environments are exposed to fluctuating mechanical forces. While cells can activate the cortical migration machinery to escape from undesirable compressive stress, the consequence to less motile cells and of prolonged extensive confinement is yet to be uncovered. Here, we demonstrate that nuclear deformation generated by axial confinement triggers a specific form of regulated cell death – ferroptosis. We show that axial confinement is sensed by the nucleus and results in Drp1-dependent mitochondrial fragmentation and mitochondrial ROS accumulation. Meanwhile, we detect cPLA2 translocation to mitochondria. These mitochondrial ROS accumulation and arachidonic acid production concertedly lead to lipid peroxidation and evoke ferroptosis. Interestingly, we find in osteoarthritis, a disease intimately associated with mechanical overloading and inflammation, characteristics of confinement-induced ferroptosis including mitochondrial localization of cPLA2 and high ROS. Together, our findings unveil a pivotal role of cell nucleus and mitochondria in linking mechanical confinement with cell death, highlighting the orchestration of Drp1 and cPLA2 in confinement-induced ferroptosis. A groundbreaking study reveals how physical confinement triggers ferroptosis. It finds the nucleus acts as a mechanosensor, orchestrating Drp1 and cPLA2 that leads to mitochondrial dysfunction and ultimately, cell death.
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DOI
PubMed
高影响因子
Bio-Design and Manufacturing
·
2021
·Vol. 4
·期 4
·776-789
·
IF 6.302
Fei Panyu,Ding Haibo,Duan Yu,Wang Xinyi,Hu Wei,Wu Peng,Wei Mengxiao,Peng Zhengchun,Gu Zhongze,Chen Wei
Biophysical restrictions regulate protein diffusion, nucleus deformation, and cell migration, which are all universal and important processes for cells to perform their biological functions. However, current technologies addressing these multiscale questions are extremely limited. Herein, through two-photon polymerization (TPP), we present the precise, low-cost, and multiscale microstructures (micro-fences) as a versatile investigating platform. With nanometer-scale printing resolution and multiscale scanning capacity, TPP is capable of generating micro-fences with sizes of 0.5–1000 μm. These micro-fences are utilized as biophysical restrictions to determine the fluidity of supported lipid bilayers (SLB), to investigate the restricted diffusion of Src family kinase protein Lck on SLB, and also to reveal the mechanical bending of cell nucleus and T cell climbing ability. Taken together, the proposed versatile and low-cost micro-fences have great potential in probing the restricted dynamics of molecules, organelles, and cells to understand the basics of physical biology. Graphic abstract
研究领域:
细胞生物学
·
生物物理学
·
微制造
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）