Soft glassy rheology of single cells with pathogenic protein aggregates.

A correlation between the mechanical properties of cells and various diseases has been emerging in recent years. Atomic force microscopy (AFM) has been widely used to measure a single cell's apparent Young's modulus by treating it as a fully elastic object. More recently, quantitative characterization of the complete viscoelasticity of single cells has become possible.

Protocol for measuring mechanical properties of live cells using atomic force microscopy.

Atomic force microscope (AFM) is a powerful and versatile tool to determine the physical properties of cells. The force-distance curves obtained from AFM experiments can be used to determine the stiffness and viscoelastic properties of cells. Here, we present a protocol for the determination of viscoelasticity from live cells such as Drosophila hemocytes or mouse embryonic stem cells using AFM.

Viscoelasticity of single folded proteins using dynamic atomic force microscopy.

The advent of atomic force microscopy, along with optical tweezers, ushered in a new field of single molecule force spectroscopy, wherein the response of a single protein or a macromolecule to external mechanical perturbations is measured. Controlled forces ranging from pN to nN are applied to measure the unfolding force distribution of a single protein domain. In a clamp type experiment, the folded protein is subjected to a constant force to measure the unfolding time distribution.

Direct and Simultaneous Measurement of the Stiffness and Internal Friction of a Single Folded Protein.

The nanomechanical response of a folded single protein, the natural nanomachine responsible for myriad biological processes, provides insight into its function. The conformational flexibility of a folded state, characterized by its viscoelasticity, allows proteins to adopt different shapes to perform their function. Despite efforts, its direct measurement has not been possible so far.

Fluorescence correlation spectroscopy based insights into diffusion in electrochemical energy systems.

Fluorescence Correlation Spectroscopy, a commonly used technique for measuring diffusion of biomolecules and tracer dyes in different solvents, is employed to characterise the local transport properties in battery electrolytes. Diffusion of ions, a major limiting factor in battery capacity and charging rates, depends on the local interactions and structuredness of the electrolytic species. Structuredness in the electrolyte results from typical solvation behaviour of diffusing ions/molecules leading to long-range interactions.

Polymerization kinetics of tubulin from mung seedlings modeled as a competition between nucleation and GTP-hydrolysis rates.

Microtubules (MTs) form physiologically important cytoskeletal structures that are assembled by tubulin polymerization in nucleation- and guanosine triphosphate (GTP)-dependent manner. GTP hydrolysis competes with the addition of monomers, to determine the GTP-cap size, and the onset of shrinkage, which alternates with growth. Multiple theoretical models of MT polymerization dynamics have been reconciled to the kinetics of animal brain tubulins, but more recently, rapid kinetics seen in Arabidopsis tubulin polymerization suggest the need to sample a wider diversity in tubulin polymerization kinetics and reconcile it to theory.

Quantitative Elasticity of Flexible Polymer Chains Using Interferometer-Based AFM.

We estimate the elasticity of single polymer chains using atomic force microscope (AFM)-based oscillatory experiments. An accurate estimate of elasticity using AFM is limited by assumptions in describing the dynamics of an oscillating cantilever. Here, we use a home-built fiber-interferometry-based detection system that allows a simple and universal point-mass description of cantilever oscillations.

Translational Diffusion of a Fluorescent Tracer Molecule in Nanoconfined Water.

Diffusion of tracer dye molecules in water confined to the nanoscale is an important subject with a direct bearing on many technological applications. It is not yet clear, however, if the dynamics of water in hydrophilic as well as hydrophobic nanochannels remains bulk-like. Here, we present diffusion measurement of a fluorescent dye molecule in water confined to the nanoscale between two hydrophilic surfaces whose separation can be controlled with a precision of less than a nm.

Resistive Switching in HfO/LaSrMnO Heterostructures: An Intriguing Case of Low H-Field Susceptibility of an E-Field Controlled Active Interface.

High-performance nonvolatile resistive random access memories (ReRAMs) and their small stimuli control are of immense interest for high-speed computation and big-data processing in the emerging Internet of Things (IoT) arena. Here, we examine the resistive switching (RS) behavior in growth-controlled HfO/LaSrMnO (LSMO) heterostructures and their tunability in a low magnetic field. It is demonstrated that oxygen-deficient HfO films show bipolar switching with a high on/off ratio, stable retention, as well as good endurance owing to the orthorhombic-rich phase constitution and charge (de)trapping-enabled Schottky-type conduction.

Validity of point-mass model in off-resonance dynamic atomic force microscopy.

The quantitative measurement of viscoelasticity of nano-scale entities is an important goal of nanotechnology research and there is considerable progress with advent of dynamic atomic force microscopy. The hydrodynamics of cantilever, the force sensor in AFM measurements, plays a pivotal role in quantitative estimates of nano-scale viscoelasticity. The point-mass (PM) model, wherein the AFM cantilever is approximated as a point-mass with mass-less spring is widely used in dynamic AFM analysis and its validity, particularly in liquid environments, is debated.

Interaction of chloramphenicol with titin I27 probed using single-molecule force spectroscopy.

Titin is a giant elastic protein which is responsible for passive muscle stiffness when muscle sarcomeres are stretched. Chloramphenicol, besides being a broad-spectrum antibiotic, also acts as a muscle relaxant. Therefore, it is important to study the interaction between titin I27 and chloramphenicol.

Mechanism of Adhesion of Natural Polymer Coatings to Chemically Modified Siloxane Polymer.

Surface coatings play an important role in improving the performance of biomedical implants. Polydimethylsiloxane (PDMS) is a commonly used material for biomedical implants, and surface-coated PDMS implants frequently face problems such as delamination or cracking of the coating. In this work, we have measured the performance of nano-coatings of the biocompatible protein polymer silk fibroin (SF) on pristine as well as modified PDMS surfaces.

The nano-scale viscoelasticity using atomic force microscopy in liquid environment.

We measured viscoelasticity of two nanoscale systems, single protein molecules and molecular layers of water confined between solid walls. In order to quantify the viscoelastic response of these nanoscale systems in liquid environment, the measurements are performed using two types of atomic force microscopes (AFMs), which employ different detection schemes to measure the cantilever response. We used a deflection detection scheme, available in commercial AFMs, that measures cantilever bending and a fibre-interferometer based detection which measures cantilever displacement.

Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness.

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of , similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency.

Differential tissue stiffness of body column facilitates locomotion of on solid substrates.

The bell-shaped members of the Cnidaria typically move around by swimming, whereas the polyp can perform locomotion on solid substrates in an aquatic environment. To address the biomechanics of locomotion on rigid substrates, we studied the 'somersaulting' locomotion in We applied atomic force microscopy to measure the local mechanical properties of 's body column and identified the existence of differential Young's modulus between the shoulder region versus rest of the body column at 3:1 ratio. We show that somersaulting primarily depends on differential tissue stiffness of the body column and is explained by computational models that accurately recapitulate the mechanics involved in this process.

A new method for measurement and quantification of tracer diffusion in nanoconfined liquids.

We report development of a novel instrument to measure tracer diffusion in water under nanoscale confinement. A direct optical access to the confinement region, where water is confined between a tapered fiber and a flat substrate, is made possible by coating the probe with metal and opening a small aperture (0.1 μm-1 μm) at its end.

Excess area dependent scaling behavior of nano-sized membrane tethers.

Thermal fluctuations in cell membranes manifest as an excess area ([Formula: see text]) which governs a multitude of physical process at the sub-micron scale. We present a theoretical framework, based on an in silico tether pulling method, which may be used to reliably estimate [Formula: see text] in live cells. We perform our simulations in two different thermodynamic ensembles: (i) the constant projected area and (ii) the constant frame tension ensembles and show the equivalence of our results in the two.

The effect of boundary slippage and nonlinear rheological response on flow of nanoconfined water.

The flow of water confined to nanometer-sized pores is central to a wide range of subjects from biology to nanofluidic devices. Despite its importance, a clear picture about nanoscale fluid dynamics is yet to emerge. Here we measured dissipation in less than 25 nm thick water films and it was found to decrease for both wetting and non-wetting confining surfaces.

The Template Determines Whether Chemically Identical Nanoparticle Scaffolds Show Elastic Recovery or Plastic Failure.

Subtle variations in the preparation of ice-templated nanoparticle assemblies yield monoliths that are chemically identical but exhibit qualitatively different mechanical behavior. We ice template aqueous dispersions to prepare macroporous monoliths largely comprising silica nanoparticles held together by a crosslinked polymer mesh. When the polymer is crosslinked in the presence of ice crystals, we obtain an elastic sponge that is capable of recovery after imposition of large compressive strains (up to 80%).

Viscoelasticity and shear thinning of nanoconfined water.

Understanding flow properties and phase behavior of water confined to nanometer-sized pores and slits is central to a wide range of problems in science, such as percolation in geology, lubrication of future nano-machines, self-assembly and interactions of biomolecules, and transport through porous media in filtration processes. Experiments with different techniques in the past have reported that viscosity of nanoconfined water increases, decreases, or remains close to bulk water. Here we show that water confined to less than 20-nm-thick films exhibits both viscoelasticity and shear thinning.

A new tuning fork-based instrument for oscillatory shear rheology of nano-confined liquids.

We present a new method to measure rheological response of liquids confined to nano-scale which exhibit a considerable slow-down in dynamics compared to bulk liquids. The method relies on using a tuning fork force sensor that has stiffness of 5.5 × 10(4) N/m to avoid thermal noise.

Probing the role of chain length on the diffusion dynamics of π-conjugated polymers by fluorescence correlation spectroscopy.

We investigate the role of the chain length and molecular weight distribution on the diffusion dynamics of freshly synthesized MEH-PPV polymer chains. For the above purpose, a new technique based on combination of size exclusion chromatography (SEC) with fluorescence correlation spectroscopy (FCS) is developed to probe the diffusion dynamics of a narrow molecular weight distribution of fractionated samples of 20-500 kDa. The narrow dispersed samples were characterized by absorbance, emission, and time-resolved fluorescence decay techniques.

Dynamic solidification in nanoconfined water films.

Mechanical properties of nanoconfined water layers are still poorly understood and continue to create controversy, despite their importance for biology and nanotechnology. We report on dynamic nanomechanical measurements of water films compressed to a few single molecular layers. We show that the mechanical properties of nanoconfined water layers change significantly with their dynamic state.

Simultaneous normal and shear measurements of nanoconfined liquids in a fiber-based atomic force microscope.

We have developed an atomic force microscopy (AFM) technique that can perform simultaneous normal and shear stiffness measurements of nanoconfined liquids with angstrom-range amplitudes. The AFM technique is based on a fiber-interferometric, small-amplitude, off-resonance AFM. This AFM is capable of providing linear quasistatic measurements of the local mechanical properties of confined liquid layers while only minimally disturbing the layers themselves.