The atomic force microscope is broadly used to study the morphology of cells1–5 but it can also probe the mechanics of cells. It is now known that cancerous cells may have different mechanical properties than normal cells6–8 but the reasons for these differences are poorly understood9. Here we report quantitatively the differences between normal and cancerous human cervical epithelial cells by considering the brush layer on the cell surface. These brush layers, which consist mostly of microvilli, microridges, and cilia are important for interacting with the environment. Deformation force curves obtained from cells in vitro are processed according to the 'brush on soft cell model 10. We found that normal cells have brushes with one length while cancerous cells displayed long and short brushes with significantly different densities. The observed differences suggest that brush layers should be taken into account when characterizing the cell surface by mechanical means.

Observation of a brush on the cell surface with the atomic force microscopy ͑AFM͒ in vitro is reported. The number of methods to study brushes that coat living cells is limited despite their biological importance. Moreover, it is important to take into account the brush layer when studying cell mechanics. Here the authors present an AFM method to detect the length and grafting density of the brush on viable cells with resolution that considerably surpasses any existing method. The authors demonstrate this method using cultured human cervical epithelial cells, but it can be applied to any type of cell.

Recently a periplasmic glucose/galactose binding protein, GGRQ26C, immobilized on a gold surface has been used as an active part of a glucose biosensor based on quartz microbalance technique. However the nature of the glucose detection was not clear. Here we have found that the receptor protein film immobilized on the gold surface increases its rigidity when glucose is added, which explains the unexpected detection signal. To study the rigidity change, we developed a new fast and simple method based on using atomic force microscopy (AFM) in tapping mode. The method was verified by explicit measurements of the Young's modulus of the protein film by conventional AFM methods. Since there are a host of receptors that undergo structural change when activated by ligand, AFM can play a key role in the development and/or optimization of biosensors based on rigidity changes in biomolecules.