A cost-effective method that integrates high-resolution morphology using an atomic force microscope and immunofluorescence imaging for measuring the local mechanical properties of a cell was developed. By considering the normal indentation conditions and the distribution of the underlying cytoskeleton, a criterion for selecting indentation sites was proposed. PC-12 cells cultivated under normal and high D-glucose medium are employed to demonstrate the applicability of the proposed method. The apparent Young's modulus for each indentation site was estimated by fitting the data with a pyramidal punch contact mechanics model. The results showed that the cell bodies cultivated in the high D-glucose medium were higher but their growth cones were shorter than those cultivated in a normal medium. The Young's moduli of the growth cones were positively correlated with the density of the actin filament in the cytoskeleton. The Young's moduli at the growth cone and the nucleus region of cells cultivated in the high D-glucose medium were higher and lower, respectively, than those of the control group. The results demonstrated the integrated method could correlate local mechanical properties and distribution of actin filament of the growth cone of PC-12 cell.
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