The Stochastic Dynamics of an Array of Atomic Force Microscopes in a Viscous Fluid

We consider the stochastic dynamics of an array of two closely spaced atomic force microscope cantilevers in a viscous fluid for use as a possible biomolecule sensor. The cantilevers are not driven externally, as is common in applications of atomic force microscopy, and we explore the stochastic cantilever dynamics due to the constant buffeting of fluid particles by Brownian motion. The stochastic dynamics of two adjacent cantilevers are correlated due to long range effects of the viscous fluid. Using a recently proposed thermodynamic approach the hydrodynamic correlations are quantified for precise experimental conditions through deterministic numerical simulations. Results are presented for an array of two readily available atomic force microscope cantilevers. It is shown that the force on a cantilever due to the fluid correlations with an adjacent cantilever is more than 3 times smaller than the Brownian force on an individual cantilever. Our results indicate that measurements of the correlations in the displacement of an array of atomic force microscopes can detect piconewton forces with microsecond time resolution.Comment: 7 page article with 11 images submitted to the International Journal of Nonlinear Mechanic

Nucleosome conformation dictates the histone code

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP: histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher-order factors. Here, we show that the [BPTF PHD finger and bromodomain: histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the 'histone code' concept and interrogate it at the nucleosome level