Beedle Amy E M, Jaganathan Anuja, Albajar-Sigalés Aina, Yavitt F Max, Bera Kaustav, Andreu Ion, Granero-Moya Ignasi, Zalvidea Dobryna, Kechagia Zanetta, Wiche Gerhard, Trepat Xavier, Ivaska Johanna, Anseth Kristi S, Shenoy Vivek B, Roca-Cusachs Pere
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.
Department of Physics, King's College London, London WC2R 2LS, UK.
bioRxiv. 2023 Nov 11:2023.11.08.566191. doi: 10.1101/2023.11.08.566191.
The cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate not only the transmission of these signals, but also their timing and duration. Such timescale regulation is well described for fluctuating chemical signals, but if and how it applies to mechanical signals reaching the nucleus is still unknown. Here we demonstrate that the formation of fibrillar adhesions locks the nucleus in a mechanically deformed conformation, setting the mechanical response timescale to that of fibrillar adhesion remodelling (~1 hour). This process encompasses both mechanical deformation and associated mechanotransduction (such as via YAP), in response to both increased and decreased mechanical stimulation. The underlying mechanism is the anchoring of the vimentin cytoskeleton to fibrillar adhesions and the extracellular matrix through plectin 1f, which maintains nuclear deformation. Our results reveal a mechanism to regulate the timescale of mechanical adaptation, effectively setting a low pass filter to mechanotransduction.
细胞核持续暴露于化学和机械性质的外部信号中。为确保细胞做出适当反应，细胞不仅需要调节这些信号的传递，还需要调节其时间和持续时间。对于波动的化学信号，这种时间尺度调节已得到充分描述，但它是否适用于到达细胞核的机械信号以及如何适用仍然未知。在这里，我们证明纤维状黏附的形成将细胞核锁定在机械变形构象中，将机械反应时间尺度设定为纤维状黏附重塑的时间尺度（约1小时）。这个过程包括机械变形和相关机械转导（如通过YAP），以响应增加和减少的机械刺激。潜在机制是波形蛋白细胞骨架通过网蛋白1f锚定到纤维状黏附和细胞外基质，从而维持核变形。我们的结果揭示了一种调节机械适应时间尺度的机制，有效地为机械转导设置了一个低通滤波器。
