Advanced dynamic atomic force microscopy methods for high-resolution in vitro biomechanical assays of cancer cells

人体细胞的机械性能会因外来生物或疾病的入侵而发生显著变化。例如，最近的研究清楚地表明，肿瘤细胞的机械特性（弹性、粘附性）在即将转移时会发生显著变化。因此，活细胞的弹性和粘附性测量可以用作其健康状况的指标或作为即将发生的疾病的早期指标。这种生物力学测定还可以提供对潜在疾病机制的有价值的见解，并有助于发现靶向癌细胞细胞骨架的抗癌治疗。拟议的工作涉及使用原子力显微镜进行癌细胞的快速，高分辨率，微创，生物力学测定的先进方法的发展。与许多现有的细胞生物力学测定方法相反，所提出的方法将提供癌细胞的机械特性的定量图或分布。通过精细地分辨活癌细胞的局部纳米力学性质的变化，将获得关于癌症生物力学的大量新的诊断信息。这些新的信息可能对早期癌症诊断、抗癌药物以及对癌细胞生物物理学/生物力学更好的基本理解非常有用。

Human cell mechanical properties can change significantly due to invasion of foreign organisms or disease. For example, recent research has clearly shown that the mechanical properties (elasticity, adhesion) of tumor cells change dramatically when they are about to metastasize. Thus elasticity and adhesion measurements of a living cell can be used as indicators of its health or as early indicators of impending disease. Such biomechanical assays can also offer valuable insight into the underlying disease mechanisms and aid in the discovery of anti-cancer treatments that target the cytoskeleton of cancer cells. The proposed work deals with the development of advanced methods using the Atomic Force Microscope for fast, high resolution, minimally invasive, biomechanical assays of cancer cells. As opposed to many existing methods of cell biomechanical assays, the proposed methods will provide quantitative maps or distributions of mechanical properties of cancer cells. By finely resolving variations of local nanomechanical properties of living cancer cells a wealth of new diagnostic information on cancer biomechanics will become available. Such new information could be widely useful for early cancer diagnosis, anti-cancer drugs, and for a better fundamental understanding of cancer cell biophysics/biomechanics.