Charge regulation indicates water expulsion from silica surface by cesium cations.

Hypothesis: Since the discovery of the Hofmeister effect in 1888, the varied propensity of ions to proteins, DNA and other surfaces has motivated research aimed at deciphering the underlying ion specific adsorption mechanism. Experimental and numerical studies have shown that in agreement with Collins' heuristic law of matching water affinity, weakly hydrated (chaotropic) ions adsorb preferentially to hydrophobic surfaces. Here, we show that this preference is driven by expulsion of bound water molecules from the surface by the adsorbing ions.

Effective Stiffness of Hydrated Atomic Force Microscopy Tips.

When generating force curves with atomic force microscopy (AFM), the conventional assumption is that the silicon tip's apex is infinitely stiffer than the force gradient acting between the apex and test object. Although true for measurements in vacuum or at long distances, we show this assumption fails badly at short distances in aqueous environments. In this case, the effective apex is an adsorbed water molecule, bound by a weak O-H···O-H H-bond.

Thermodynamics of Charge Regulation near Surface Neutrality.

The interaction between two adjacent charged surfaces immersed in aqueous solution is known to be affected by charge regulation─the modulation of surface charge as two charged surfaces approach each other. This phenomenon is particularly important near surface neutrality where the stability of objects such as colloids or biomolecules is jeopardized. Focusing on this ubiquitous case, we elucidate the underlying thermodynamics and show that charge regulation is governed in this case by surface entropy.

A constant-frequency feedback loop for non-contact frequency-modulated atomic force microscopy via root locus: Implemented on a single-board field-programmable gate array device.

Non-contact, frequency modulated atomic force microscopy is often operated in the constant-frequency mode to obtain a height map of the sample's surface. Once linearized, the dynamics of the constant-frequency closed-loop system are reduced to a single transfer function. By modifying the bandwidth of this transfer function, a tradeoff is achieved between image noise and imaging speed.

Observation of branched flow of light.

When waves propagate through a weak disordered potential with correlation length larger than the wavelength, they form channels (branches) of enhanced intensity that keep dividing as the waves propagate. This fundamental wave phenomenon is known as branched flow. It was first observed for electrons and for microwave cavities, and it is generally expected for waves with vastly different wavelengths, for example, branched flow has been suggested as a focusing mechanism for ocean waves, and was suggested to occur also in sound waves and ultrarelativistic electrons in graphene.

Sequence-Dependent Deviations of Constrained DNA from Canonical B-Form.

Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly(dA)-poly(dT), poly(dG)-poly(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure.

Common Source of Cryoprotection and Osmoprotection by Osmolytes.

While recent studies clarify the effect of osmolytes on Coulomb interaction at elevated concentrations of salt, little is known about the way osmolytes affect the same interaction in cryoprotection. In this Communication we explore the effect of cold on the interaction between two charged surfaces immersed in ternary solution containing salt and osmolyte and find that the effect of cold parallels that of excess salt, i.e.

Multiply Modified Repeating DNA Templates for Production of Novel DNA-Based Nanomaterial.

Here, we report synthesis of long (thousands of base pairs), uniform double-stranded (ds) DNA comprising short (6-15 base pairs) tandem repeats. The synthesis method is based on self-assembly of short (6-15 bases) half-complementary 5'-end phosphorylated single-stranded oligonucleotides into long ds polymer molecules and covalent association of the oligonucleotide fragments in the polymer by DNA ligase to yield complete non-nicked ds DNA. The method is very flexible in regard to the sequence of the oligonucleotides and their length.

Zwitterionic Osmolytes Resurrect Electrostatic Interactions Screened by Salt.

Many cells synthesize significant quantities of zwitterionic osmolytes to cope with the osmotic stress induced by excess salt. In addition to their primary role in balancing osmotic pressure, these osmolytes also help stabilize protein structure and restore enzymatic activity compromised by high ionic strength. This osmoprotective effect has been studied extensively, but its electrostatic aspects have somehow escaped the mainstream.

Three-Dimensional Characterization of Layers of Condensed Gas Molecules Forming Universally on Hydrophobic Surfaces.

Understanding the solvation layer of hydrophobic surfaces is essential for elucidating the interaction between hydrophobic surfaces in aqueous solutions. Despite their importance, little is known on these layers due to the lack of lateral resolution in spectroscopic or scattering experiments and probe instability in the static scanning probe methods used in most experiments. Using a high-resolution FM-AFM with stiff cantilevers and hydrophilic tips, we overcome this instability to provide the first detailed 3d maps of the solvation/hydration layer of two archetypal hydrophobic surfaces: graphite (HOPG) and self-assembled fluoro-alkane monolayer (FDTS).

Hydration Structure of a Single DNA Molecule Revealed by Frequency-Modulation Atomic Force Microscopy.

Hydration interaction shapes biomolecules and is a dominant intermolecular force. Mapping the hydration patterns of biomolecules is therefore essential for understanding molecular processes in biology. Numerous studies have been devoted to this challenge, but current methods cannot map the hydration of single biomolecules, let alone do so under physiological conditions.

Regulation of Surface Charge by Biological Osmolytes.

Osmolytes, small molecules synthesized by all organisms, play a crucial role in tuning protein stability and function under variable external conditions. Despite their electrical neutrality, osmolyte action is entwined with that of cellular salts and protons in a mechanism only partially understood. To elucidate this mechanism, we utilize an ultrahigh-resolution frequency modulation-AFM for measuring the effect of two biological osmolytes, urea and glycerol, on the surface charge of silica, an archetype protic surface with a pK value similar to that of acidic amino acids.

New Information on the Hydrophobic Interaction Revealed by Frequency Modulation AFM.

Using ultrahigh resolution atomic force microscopy (AFM) operated in frequency modulation mode, we extend existing measurements of the force acting between hydrophobic surfaces immersed in water in three essential ways. (1) The measurement range, which was previously limited to distances longer than 2-3 nm, is extended to cover all distances, down to contact. The measurements disclose that the long-range attraction observed also by conventional techniques, turns at distances shorter than 1-2 nm into pronounced repulsion.

Autopilot for frequency-modulation atomic force microscopy.

One of the most challenging aspects of operating an atomic force microscope (AFM) is finding optimal feedback parameters. This statement applies particularly to frequency-modulation AFM (FM-AFM), which utilizes three feedback loops to control the cantilever excitation amplitude, cantilever excitation frequency, and z-piezo extension. These loops are regulated by a set of feedback parameters, tuned by the user to optimize stability, sensitivity, and noise in the imaging process.

Accurate, explicit formulae for higher harmonic force spectroscopy by frequency modulation-AFM.

The nonlinear interaction between an AFM tip and a sample gives rise to oscillations of the cantilever at integral multiples (harmonics) of the fundamental resonance frequency. The higher order harmonics have long been recognized to hold invaluable information on short range interactions but their utilization has thus far been relatively limited due to theoretical and experimental complexities. In particular, existing approximations of the interaction force in terms of higher harmonic amplitudes generally require simultaneous measurements of multiple harmonics to achieve satisfactory accuracy.

On the limited recognition of inorganic surfaces by short peptides compared with antibodies.

The vast potential applications of biomolecules that bind inorganic surfaces led mostly to the isolation of short peptides that target selectively specific materials. The demonstrated differential affinity toward certain surfaces created the impression that the recognition capacity of short peptides may match that of rigid biomolecules. In the following, we challenge this view by comparing the capacity of antibody molecules to discriminate between the (100) and (111A) facets of a gallium arsenide semiconductor crystal with the capacity of short peptides to do the same.

The governing role of surface hydration in ion specific adsorption to silica: an AFM-based account of the Hofmeister universality and its reversal.

AFM measurements of the force acting between silica surfaces in the presence of varied alkali chloride salts and pH's elucidate the origin of the Hofmeister adsorption series and its reversal. At low pH, electrostatics is shown to be insignificant. The preferential adsorption of Cs(+) to the silica surface is traced to the weak hydration of neutral silanols and the resulting hydrophobic expulsion of weakly hydrated ions from bulk solution to the interface.

Mixed alkanethiol monolayers on submicrometric gold patterns: a controlled platform for studying cell-ligand interactions.

Nanoscale organization of surface ligands often has a critical effect on cell-surface interactions. We have developed an experimental system that allows a high degree of control over the 2-D spatial distribution of ligands. As a proof of concept, we used the developed system to study how T-cell activation is independently affected by antigen density and antigen amount per cell.

Hollow nanoneedle array and its utilization for repeated administration of biomolecules to the same cells.

We present a novel hollow nanoneedle array (NNA) device capable of simultaneously delivering diverse cargo into a group of cells in a culture over prolonged periods. The silica needles are fed by a common reservoir whose content can be replenished and modified in real time while maintaining contact with the same cells. The NNA, albeit its submicrometer features, is fabricated in a silicon-on-insulator wafer using conventional, large scale, silicon technology.

Electrically controlled molecular recognition harnessed to activate a cellular response.

Seamless embedment of electronic devices in biological systems is expected to add the outstanding computing power, memory, and speed of electronics to the biochemical toolbox of nature. Such amalgamation requires transduction of electronic signals into biochemical cues that affect cells. Inspired by biology, where pathways are directed by molecular recognition, we propose and demonstrate a generic electrical-to-biological transducer comprising a two-state electronic antigen and a chimeric cell receptor engineered to bind the antigen exclusively in its "on" state.

Effect of cation size and charge on the interaction between silica surfaces in 1:1, 2:1, and 3:1 aqueous electrolytes.

Application of two complementary AFM measurements, force vs separation and adhesion force, reveals the combined effects of cation size and charge (valency) on the interaction between silica surfaces in three 1:1, three 2:1, and three 3:1 metal chloride aqueous solutions of different concentrations. The interaction between the silica surfaces in 1:1 and 2:1 salt solutions is fully accounted for by ion-independent van der Waals (vdW) attraction and electric double-layer repulsion modified by cation specific adsorption to the silica surfaces. The deduced ranking of mono- and divalent cation adsorption capacity (adsorbability) to silica, Mg(2+) < Ca(2+) < Na(+) < Sr(2+) < K(+) < Cs(+), follows cation bare size as well as cation solvation energy but does not correlate with hydrated ionic radius or with volume or surface ionic charge density.

From repulsion to attraction and back to repulsion: the effect of NaCl, KCl, and CsCl on the force between silica surfaces in aqueous solution.

The force between silica surfaces in NaCl, KCl and CsCl aqueous solutions is studied at pH 5.5 using an atomic force microscope (AFM). As ion concentration is increased, more cations adsorb to the negatively charged silica, gradually neutralizing the surface charge, hence, suppressing the electrostatic double layer repulsion and revealing van der Waals attraction.

Measuring changes in surface potential as two charged bodies approach in electrolyte solution.

Combining atomic force microscopy with an ion-sensitive field effect transistor we provide a novel potentiometer capable of measuring a surface potential change as small as 100 microV at 0.2 nm spatial resolution when two charged bodies approach in an electrolyte solution. The surface potential measured when two silica surfaces approach deviates significantly from values inferred indirectly by conventional analysis of force curves.

A two-state electronic antigen and an antibody selected to discriminate between these states.

Inspired by biology where pathways are triggered and suppressed by specific binding of two molecules, we realize a functional interface between electronics and biology by replacing one of the pair molecules with a two-state "electronic antigen" device comprising a hydroquinone monolayer assembled on gold, and choosing for the pair molecule an antibody that discriminates between the two electrically selected redox states of the monolayer. Application of an oxidative +0.6 V pulse to the antigen switches it to its benzoquinone state where antibodies bind the layer.