近日，美国加州大学教授Johannes Schöneberg及其课题组的研究开发出了基于四维晶格光片显微镜数据的全细胞粒子数字孪生模拟。2026年6月30日出版的《细胞》发表了这项成果。
该研究组引入了一个全细胞数字双胞胎框架，该框架集成了二维（4D）（x, y， z和t）晶格光片显微镜和基于粒子的反应-扩散模拟，以模拟中尺度细胞内细胞器动力学。利用活Cal27细胞的荧光显微镜数据，该研究团队构建了空间分辨的数字双胞胎，包括线粒体网络、微管网络、动力蛋白和动力蛋白马达、质膜和核核。线粒体动力学包括离子/裂变重塑、扩散和沿微管运动驱动的主动运输。他们的模拟重现了控制和两种微管扰动条件下线粒体动力学的实验趋势，证明了无需重新参数化的预测能力。然后，该课题组主题应力模拟，以预测出现的核周围线粒体细胞分裂。至关重要的是，这些模拟揭示了微管拓扑结构作为这种重组的结构门，表明如果没有允许的丝连接，仅靠逆行运动动力学的调高不足以驱动纤凝。这个数字双胞胎框架提供了一种以可解释和生物学为基础的方式研究细胞内动力学和扰动效应的方法。
附：英文原文
Title: Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data
Author: Eric Arkfeld, Zichen Wang, Hiroyuki Hakozaki, Johannes Schneberg
Issue&Volume: 2026-06-30
Abstract: We introduce a whole-cell digital twin framework that integrates four-dimensional (4D) (x, y, z, and t) lattice light-sheet microscopy with particle-based reaction-diffusion simulations in ReaDDy to model mesoscale intracellular organelle dynamics. Using fluorescence microscopy data from live Cal27 cells, we construct spatially resolved digital twins incorporating mitochondrial networks, microtubule networks, dynein and kinesin motors, the plasma membrane, and the nucleus. Mitochondrial dynamics include fusion/fission remodeling, diffusion, and motor-driven active transport along microtubules. Our simulations reproduce experimental trends in mitochondrial dynamics across control and two microtubule-perturbed conditions, demonstrating predictive capability without reparameterization. We then use stress-mimicking to predict emergent perinuclear mitochondrial clustering. Crucially, these simulations reveal that microtubule topology acts as a structural gate for this reorganization, demonstrating that upregulated retrograde motor kinetics alone are insufficient to drive clustering without permissive filament connectivity. This digital twin framework provides an approach for investigating intracellular dynamics and perturbation effects in an interpretable and biologically grounded manner.
DOI: 10.1016/j.cell.2026.06.010
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00697-5
期刊信息
Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85
官方网址：https://www.cell.com/
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