Auditory Mechanics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Nanotechnol. 2012 Nov;7(11):733-6. doi: 10.1038/nnano.2012.163. Epub 2012 Sep 30.
The atomic force microscope can detect the mechanical fingerprints of normal and diseased cells at the single-cell level under physiological conditions. However, atomic force microscopy studies of cell mechanics are limited by the 'bottom effect' artefact that arises from the stiff substrates used to culture cells. Because cells adhered to substrates are very thin, this artefact makes cells appear stiffer than they really are. Here, we show an analytical correction that accounts for this artefact when conical tips are used for atomic force microscope measurements of thin samples. Our bottom effect cone correction (BECC) corrects the Sneddon's model, which is widely used to measure Young's modulus, E. Comparing the performance of BECC and Sneddon's model on thin polyacrylamide gels, we find that although Sneddon's model overestimates E, BECC yields E values that are thickness-independent and similar to those obtained on thick regions of the gel. The application of BECC to measurements on live adherent fibroblasts demonstrates a significant improvement on the estimation of their local mechanical properties.
原子力显微镜可以在生理条件下检测单细胞水平上正常和患病细胞的机械指纹。然而，细胞力学的原子力显微镜研究受到“底部效应”伪影的限制，这种伪影是由用于培养细胞的刚性基底引起的。由于附着在基底上的细胞非常薄，这种伪影使得细胞看起来比实际更硬。在这里，我们展示了一种分析校正方法，当使用锥形尖端进行原子力显微镜对薄样品的测量时，可以校正该伪影。我们的底部效应锥校正（BECC）校正了广泛用于测量杨氏模量 E 的 Sneddon 模型。通过比较 BECC 和 Sneddon 模型在薄聚丙烯酰胺凝胶上的性能，我们发现虽然 Sneddon 模型高估了 E，但 BECC 得到的 E 值与厚度无关，并且与凝胶的厚区域获得的值相似。BECC 在对活贴壁成纤维细胞的测量中的应用表明，它可以显著提高对其局部力学性能的估计。
