Intracellular remodeling associated with endoplasmic reticulum stress modifies biomechanical compliance of bladder cells

Cell Communication and Signaling

Research

Walter Berger¹  Endre Kiss²  Livia Gruber³  Martina Karasová⁴  Giorgia Del Favero⁴  Maximilian Jobst⁵  Bernhard Englinger⁶ 

[1] Center for Cancer Research and Comprehensive Cancer Center, Medical University Vienna, 1090, Vienna, Austria;Core Facility Multimodal Imaging, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;Department of Food Chemistry and Toxicology, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;Department of Food Chemistry and Toxicology, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;Core Facility Multimodal Imaging, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;Department of Food Chemistry and Toxicology, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;Core Facility Multimodal Imaging, University of Vienna Faculty of Chemistry, Währinger Str. 38-40, 1090, Vienna, Austria;University of Vienna, Vienna Doctoral School in Chemistry (DoSChem), Währinger Str. 42, 1090, Vienna, Austria;Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria;Center for Cancer Research and Comprehensive Cancer Center, Medical University Vienna, 1090, Vienna, Austria;

关键词: Brefeldin A;    Thapsigargin;    Cell stiffness;    Cytoskeleton;    Endoplasmic reticulum stress;    Atomic force microscopy;   

DOI  :  10.1186/s12964-023-01295-x

 received in 2023-06-16, accepted in 2023-08-23,  发布年份 2023

来源: Springer

【 摘 要 】

Bladder cells face a challenging biophysical environment: mechanical cues originating from urine flow and regular contraction to enable the filling voiding of the organ. To ensure functional adaption, bladder cells rely on high biomechanical compliance, nevertheless aging or chronic pathological conditions can modify this plasticity. Obviously the cytoskeletal network plays an essential role, however the contribution of other, closely entangled, intracellular organelles is currently underappreciated. The endoplasmic reticulum (ER) lies at a crucial crossroads, connected to both nucleus and cytoskeleton. Yet, its role in the maintenance of cell mechanical stability is less investigated. To start exploring these aspects, T24 bladder cancer cells were treated with the ER stress inducers brefeldin A (10-40nM BFA, 24 h) and thapsigargin (0.1-100nM TG, 24 h). Without impairment of cell motility and viability, BFA and TG triggered a significant subcellular redistribution of the ER; this was associated with a rearrangement of actin cytoskeleton. Additional inhibition of actin polymerization with cytochalasin D (100nM CytD) contributed to the spread of the ER toward cell periphery, and was accompanied by an increase of cellular stiffness (Young´s modulus) in the cytoplasmic compartment. Shrinking of the ER toward the nucleus (100nM TG, 2 h) was related to an increased stiffness in the nuclear and perinuclear areas. A similar short-term response profile was observed also in normal human primary bladder fibroblasts. In sum, the ER and its subcellular rearrangement seem to contribute to the mechanical properties of bladder cells opening new perspectives in the study of the related stress signaling cascades.AnQ6eoaFZ-G6Rs7Kzp4dpwVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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