多模态机械显微镜从三维角度揭示了乳腺癌球体的机械表型。

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL APL Bioengineering Pub Date : 2024-09-09 eCollection Date: 2024-09-01 DOI:10.1063/5.0213077
Alireza Mowla, Matt S Hepburn, Jiayue Li, Danielle Vahala, Sebastian E Amos, Liisa M Hirvonen, Rowan W Sanderson, Philip Wijesinghe, Samuel Maher, Yu Suk Choi, Brendan F Kennedy
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引用次数: 0

摘要

癌细胞侵袭依赖于细胞变形能力与细胞外基质(ECM)施加的生物物理约束之间的平衡。然而,对于在三维(3D)肿瘤微环境(TME)背景下癌细胞扩散过程中局部生物力学改变的性质,目前还鲜有共识。二维(2D)模型在复制原位细胞行为方面的缺陷众所周知,而三维肿瘤微环境模型仍未得到充分利用,因为当代的力学量化工具仅限于表面测量。在这里,我们通过量化三维 TME 中癌细胞球体的局部力学来克服这一重大挑战。我们利用多模态力学显微镜,将基于光学相干显微镜的弹性成像与共聚焦荧光显微镜相结合,实现了这一目标。我们观察到,非转移性癌症球体在坚硬和柔软的环境中都没有出现侵袭,同时外围细胞弹性增强。然而,转移性癌症球体在僵硬的微环境中表现出由 ECM 介导的软化,而在软环境中,细胞开始入侵,外围软化与早期转移扩散有关。这一活体细胞三维机械分型实例证明,入侵会增加细胞在三维环境中的变形能力,说明了多模态机械显微镜在原位定量机械生物学方面的强大功能。
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Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions.

Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TMEs). While the shortcomings of two-dimensional (2D) models in replicating in situ cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology in situ.

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来源期刊
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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