实时力谱显微技术检测胰腺癌肿瘤细胞的纳米力学指纹特征

The mechanical properties of cells play an important role in the cancer progression process. To better understand the malignant transformation of the pancreatic tumor cells and the company mechanical and functional changes, it is desire to characterize the mechanical properties of cells as a biomarker for early diagnosing of the pancreatic cancer. Techniques based on quasi-static atomic force microscopy techniques can map the mechanical properties of cells, but they lack spatial and temporal resolution that is needed to observe the relative details. Here we present a real-time force spectroscopy to map the structure and mechanical properties of living cells with unprecedented spatial and temporal resolution. This study includes the following steps: (1) charactering the mechanical properties of the normal cell lines and pancreatic tumor cell lines to identify the tumor cells by their fingerprint mechanical properties; (2) characterizing isolated circulating normal and tumor cells to validate the identification of tumor cells clinically by the fingerprint mechanical properties; (3) monitoring the dynamic behaviors of the normal and tumor cells stimulated by the anti-cancer drugs and comparing the mechanical properties before and after the drug treatment. This study overcomes the drawbacks of the biophysical methods for tumor cell study and may shed light on revealing the relationship between the mechanical property and the biological function of the cells while the progression of pancreatic cancer.

细胞力学性能在癌症的演化过程中发挥着重要的作用。为研究胰腺肿瘤细胞恶性转化以及该过程中细胞力学特性与功能性的关系，亟待将细胞的力学指纹特性纳入肿瘤经典特征，并将其作为癌症早期诊断与治疗的特征指标。针对准静态原子力显微镜在表征活体细胞的力学性能中，时间和空间分辨率的不足导致细胞力学特征细节的缺失，本项目拟采用一种新的实时力谱显微镜实现在微秒时间尺度以及纳米空间尺度上来检测胰腺癌肿瘤细胞的形貌和力学指纹特性。研究包括（1）测定正常和胰腺癌肿瘤细胞系的力学指纹特性实现肿瘤细胞的特异性标识；（2）分离正常和循环肿瘤细胞实现胰腺癌肿瘤细胞特异性标识的临床验证；（3）监测正常和肿瘤细胞在抗癌药物下的动态行为及其力学性能的变化。本项目的开展将弥补当前胰腺癌研究中生物物理学研究方法的不足，对确立癌症演化过程中细胞力学特征与生物功能性之间的关系具有重要意义。

细胞力学性能在癌症的演化过程中发挥着重要的作用。为研究肿瘤细胞恶性转化以及该过程中细胞力学特性与功能性的关系，亟待将细胞的力学指纹特性纳入肿瘤经典特征，并将其作为癌症早期诊断与治疗的特征指标。针对准静态原子力显微镜在表征活体细胞的力学性能中，时间和空间分辨率的不足导致细胞力学特征细节的缺失，本项目拟采用一种新的实时力谱显微镜实现在微秒时间尺度以及纳米空间尺度上来检测肿瘤细胞的形貌和力学指纹特性。研究包括（1）测定正常和胰腺癌肿瘤细胞系的力学指纹特性实现肿瘤细胞的特异性标识；（2）测定正常和乳腺癌肿瘤细胞系的力学指纹特性实现肿瘤细胞的特异性标识；（3）监测正常和肿瘤细胞在抗癌药物下的动态行为及其力学性能的变化。本项目的开展将弥补当前肿瘤细胞研究中生物物理学研究方法的不足，对确立癌症演化过程中细胞力学特征与生物功能性之间的关系具有重要意义。