Parvini Cameron, Massey Andrew, Mezher Mazen, Cartagena-Rivera Alexander X
Section on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
ACS Nano. 2025 Aug 19;19(32):29109-29121. doi: 10.1021/acsnano.5c01873. Epub 2025 Aug 4.
Evaluating nanoscale cellular mechanics for disease biomarkers has been challenging due to the significant heterogeneity between cells and other biological structures, which reflects the variability in gene expression. Atomic force microscopy-based methods can visualize these heterogeneities with high spatiotemporal resolution; however, processing large time-dependent viscoelastic data sets is computationally expensive. Here, we introduce a novel viscoelastic method based on a modified Fourier transform, enabling multitime-scale viscoelastic analysis at drastically improved rates (over 37,386-fold) compared to traditional approaches. We used this method to quantify multitime-scale viscoelastic properties of living melanoma cells with varying degrees of malignancy. More malignant cells are softer and more fluid near the nucleus, while the leading edge is stiffer and more viscous, suggesting that regional mechanical effects are critical for enhanced migration. Cellular population heterogeneity analyses revealed that metastatic cells exhibit fluid-like viscoelastic behavior, while benign cells exhibit more solid-like behavior. This new method provides novel label-free biophysical indicators to aid in diagnostic and therapeutic approaches.
由于细胞与其他生物结构之间存在显著的异质性，而这种异质性反映了基因表达的变异性，因此评估用于疾病生物标志物的纳米级细胞力学一直具有挑战性。基于原子力显微镜的方法能够以高时空分辨率可视化这些异质性；然而，处理大量随时间变化的粘弹性数据集在计算上成本高昂。在此，我们引入一种基于改进傅里叶变换的新型粘弹性方法，与传统方法相比，能够以大幅提高的速率（超过37386倍）进行多时间尺度的粘弹性分析。我们使用这种方法量化了不同恶性程度的活黑素瘤细胞的多时间尺度粘弹性特性。恶性程度更高的细胞在细胞核附近更柔软且流动性更强，而前沿则更坚硬且粘性更大，这表明区域力学效应对于增强迁移至关重要。细胞群体异质性分析显示，转移性细胞表现出类似流体的粘弹性行为，而良性细胞表现出更类似固体的行为。这种新方法提供了新的无标记生物物理指标，有助于诊断和治疗方法。
