Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns.

Atomic force microscopy (AFM) is a powerful tool for analysing the shapes of individual molecules and the forces acting on them. AFM-based force spectroscopy provides insights into the structural and energetic dynamics of biomolecules by probing the interactions within individual molecules, or between a surface-bound molecule and a cantilever that carries a complementary binding partner. Here, we show that an AFM cantilever with an antibody tether can measure the distances between 5-methylcytidine bases in individual DNA strands with a resolution of 4 Å, thereby revealing the DNA methylation pattern, which has an important role in the epigenetic control of gene expression. The antibody is able to bind two 5-methylcytidine bases of a surface-immobilized DNA strand, and retracting the cantilever results in a unique rupture signature reflecting the spacing between two tagged bases. This nanomechanical approach might also allow related chemical patterns to be retrieved from biopolymers at the single-molecule level.

Uppsalator's acceleration.

Semiquantitative prediction of the Uppsalator (electroosmotical oscillator developed in Uppsala) under constant voltage is confirmed via numerical solution of exact nonlinear integro-differential equations in partial derivatives (PDE). Critical voltage and characteristic features of pressure and liquid flow velocity as functions of time are reproduced with high precision. In particular, the number of inflection points per period of oscillating velocity increases with growing voltage from two to six. A new feature is demonstrated. For sufficiently high voltages the Uppsalator shows normal deceleration, i.e., the oscillation period grows with voltage. However, in some supercritical range of voltages, acceleration is observed, as expressed by decrease of the oscillation period with growing voltage. Thus, the Uppsalator at constant voltage considered earlier as an impossible phenomenon represents a great challenge for experimental verification.