Computing Atomic Force Microscopy Images of Chromosomes using Polymer Simulation

Abstract

Atomic force microscopy (AFM) is a promising tool to visualize biomolecules at the sub-nanometer scale even in the liquid environment. Experimentally obtained AFM images have been compared with those simulated to reveal what is really resolved; however, such conventional images of biomolecules were usually computed by calculating equidistance surface from given atomic positions, not by calculating force. The shape of biomolecules in the simulated images were usually unnaturally rounded, and the size of molecules did not match to the actual AFM images unless the size of the probe in simulation was unrealistically smaller (about 2-50%) than used in experiments. Here, we use a polymer model of a chromosome, as a representative biomolecule, and the AFM probe, and computed isoforce surfaces upon the fiber. The oscillation of probes utilized in the dynamic mode of AFM measurements was also implemented in the simulation. The computed isoforce images were clearer than the conventional equidistance one, and the chromosomal fibers were resolved in our images. Moreover, very similar images to isoforce ones were obtained when the diameter of the probe was reduced to approximately 30% in the equidistance images, providing a theoretical explanation for the conventional use of such a small probe size in simulating AFM images of biomolecules. Thus, the probe was found to approach very close to samples beyond the estimation of the equidistance surface, contributing clear AFM images even with a relatively blunt tip.