Current Nanoscience - Volume 3, Issue 1, 2007

In this special issue of Current Nanoscience, ten invited reviews on nanomechanics of atomic and molecular systems written by expert scholars in respective fields are presented. Driven by rapid advancement both on experimental and theoretical fronts, the interest of nano-oriented scientists and engineers is now focused on elucidating precise mechanisms of the rate altering effect of externally applied force on the atomic and molecular processes which are otherwise very slow or very rare. Acceleration or deceleration of such processes in bulk materials can be achieved by changing the external parameters such as temperature or pressure but a prominent aspect of the new nanoscience is in the manipulation of individual atoms and molecules by human hands through application of force. The development of instruments such as probe microscopes and laser tweezers, among others, has enabled us to perform such experiments with unprecedented levels of precision reaching subnanometers and sub-nanonewtons in many cases. With these instruments and at these analytical scales, there is a commonality of language between researchers in different disciplines of science and engineering and many are now starting to understand the problems and achievements in otherwise distantly related fields, and importing new terminology in a much easier manner than before. Our attempt to collate expert reviews on nanoscience from diverse disciplines covering theoretical, physical, chemical and biological problems is now, therefore, made possible and it will hopefully provide a useful resource for researchers and students in a wide range of disciplines. It is the wish of the guest editors that this special issue be a catalyst for understanding the contributions made by a wide range of disciplines to the study of nanomechanics of atoms and molecules.

Many proteins react or respond to mechanical force as part of their function. Until recently the mechanical properties of proteins on the nanoscale were unknown as techniques that allowed their manipulation and measurement were not available. Over the last decade, development of robust instruments capable of picoNewton force sensitivity and sub-nanometre positional accuracy has allowed such experiments to be routinely undertaken. These experimental data, in conjunction with computational simulation methods and the development of an underpinning theoretical framework, have resulted in a greater understanding of the effects of a mechanical perturbation on biomolecules. The aim of this review is to describe how mechanical extension is thought to denature proteins, how this process differs to the intrinsic unfolding pathway and, by reference to examples, to rationalise the wide range of mechanical responses that have been observed, sometimes in proteins with very similar structures.

This paper reviews a recent progress of molecular level studies on the rigidity of surface immobilized as well as membrane bound proteins embedded in the lipid bilayer. Some details and emphasis are given to the work done in our laboratory in the last few years. Immobilization of protein molecules on a solid surface through covalent crosslinkers on one side and to the probe of the atomic force microscope on the other enabled us to pull or push a single protein molecule to specified directions. On pulling, the internal structure of the protein molecule is mechanically opened up and, on pushing, it is compressively deformed until it is flattened out. Such experiments reveal the mechanical rigidity of the folded structure of a protein molecule in two different ways. In the field of ligand-protein interaction, some merits and problems of newly introduced compression free method are discussed. When a protein molecule is embedded in a lipid membrane, information on its anchoring force to the membrane can be obtained by pulling it out from the membrane. Experiments have been done either on a lipid bilayer formed on a solid surface, or on the surface of live cells. The extraction process of membrane proteins is often accompanied by extrusion of a thin lipid tether trailing behind the target protein of the tensile force. A short review of the tether forming process from the red cell membrane surface will be given.

An atomic force microscope (AFM) under noncontact and nearcontact regions operated at room-temperature (RT) in ultrahigh vacuum, is used as a tool for topography-based atomic discrimination and lateral atomic manipulations of two intermixed atomic species on semiconductor surfaces. Noncontact AFM topography can give height difference between two intermixed atomic species. Therefore, noncontact AFM topography is a kind of atom selective image and hence can serve for atomic discrimination in simple cases. Besides, site-specific force curves provide the chemical covalent bonding forces between the tip apex and the atoms at the surface. Here, we introduced both examples related to topography-based atomic discrimination using selected Sn and Si adatoms in Sn/Si(111)-(√3×√3) surface. Recently, under nearcontact region, we found a lateral atom-interchange manipulation phenomenon at RT in Sn/Ge(111)-c(2×8) intermixed sample. This phenomenon can interchange an embedded Sn atom with a neighbor Ge atom at RT. Using the vector scan method under nearcontact region, we constructed “Atom Inlay”, that is, atom letters “Sn” consisted of 19 Sn atoms embedded in Ge(111)-c(2×8) substrate. Using these methods, now we can assemble compound semiconductor nanostructures atom-by-atom.

Force spectroscopy provides a direct approach for probing biological interactions at the single-molecule level. Tethered systems, in which flexible polymer linkers connect the interacting molecules to the surfaces of the atomic force microscope probe and sample, provide a particularly attractive platform for studying such interactions. We will review the basic physical principles of force spectroscopy measurements in these systems, and show that mechanical properties of the tether linkages allow independent determination of the bond rupture forces and the number of ruptured bonds. Forces measured in these systems obey the predictions of a Markovian model for the strength of multiple parallel bonds. Finally, we discuss the use of the dynamic force spectra of single and multiple protein-ligand bonds for determination of kinetic parameters for multivalent interactions.

Atomic force microscopy (AFM) enables high resolution topographic imaging of biological samples under near-physiological conditions. Therefore, the AFM is optimally suited for investigation of biological membranes and cell surfaces, as exemplified by studies on bacterial S-layers, purple membranes and cultured living cells. Topographic imaging allows visualizing single proteins and protein assemblies in native membranes, as well as substructures of live cells, such as cytoskeletal architecture. In addition to high-resolution imaging, the measurement of mechanical forces yields detailed insight into structure-function relationships of molecular processes in their native environment. In molecular recognition force microscopy, interaction forces between tip-bound ligands and membrane-embedded receptors can be studied under well-controlled buffer conditions and effector's concentrations. In case of low lateral density and inhomogeneous distribution of the target molecules in a cell membrane, fluorescence microscopy can help to guide the AFM tip to the membrane proteins of interest, which can subsequently be investigated by molecular recognition force microscopy.

Current topics are introduced from the results for the JST (Japan Science and Technology Agency) project for the development of the theoretical simulator of scanning probe microscopy. In spite of the crucial role played by the theoretical simulation for understanding experimental results, the theoretical calculations so far tried have been computationally very demanding. Thus one of the aim of this project is the development of efficient methods for the simulation of STM(Scanning Tunneling Microscopy), AFM(Atomic Force Microscopy) and KFM(Kelvin Force Microscopy) and their spectroscopy. Toward this purpose the simplified and efficient calculation program, as well as user friendly GUI tools for the wide range users are aimed in the JST SPM project. Another targets of the project are the development of a new frontier of the SPM simulation, in particular, for supporting experiments on biological and organic molecular systems, and for the measurement in liquids. We will discuss for the STM simulation the inelastic tunneling processes and decorated tip model. As for the AFM, we consider how to treat the dynamic cantilever motion in liquids, and the theoretical simulation for some of the protein molecules.

Cells bind to each other and to surfaces using complementary receptor-ligand pairs as an essential part of their function. The mechanical forces that build up on these bonds was assumed to weaken them until three receptor-ligand complexes were shown to form catch bonds that are instead strengthened by mechanical force. This review analyzes the experimental data for these complexes to better understand this counterintuitive effect. Models of how force affects the energy landscapes of bonds are related to the behavior of various catch bonds when subjected to force. Structural explanations of how force affects molecular structure and function are also presented and related to simulations of the effect of force on structure and to the effect of point mutations on bond function. It can be concluded that catch bonds arise when force changes the angle or distance between two domains in a way that leads to enhanced binding. However, their mechanism through which the interdomain region can influence the lifetime of the distant binding site remains unsolved since more than one proposed mechanism can explain the data. It remains possible that different catch bonds work differently or even that multiple mechanism act in the same protein.

Studies conducted during the past few decades have revealed the existence of a close connection between the mechanical responses of biological structures to stimuli and the functions of different cells, tissues and organs. The cornerstone to understanding this chain of reactions lies in a knowledge of the mechanical properties of the structures implicated in the transduction of mechanical signals. A progress in this direction has evolved rapidly in recent years, owing to innovations in the techniques used for measuring forces in the piconewton range and displacements smaller than a nanometer. In this short review, we survey the technologies that have been applied to measure the mechanical properties of one cytoskeletal component: the microtubules.

Scanning probe microscope (SPM) has been developed as a powerful tool for obtaining high resolution topographic images of biological samples in their natural aqueous environment. SPM can also be used to evaluate mechanical properties because its probe is physically in contact with the samples during measurement. To obtain cellular stiffness with SPM, we have proposed two methods: a force modulation mode and a force mapping mode. Considering the influence of the drag force of liquids, we have successfully improved the quantitative evaluation of cellular stiffness by using the force modulation mode. Experiments performed using the two methods revealed that the local stiffness of fibroblasts was not homogeneous on the cell surface but largely varied from point to point. It was revealed that spatial and temporal distributions of cellular stiffness originate in cytoskeletal distribution, mode of cellular migration, and intracellular contractile force.

We briefly review the nanomechanical studies of ultralow friction in the following carbon hybrid systems: atomic force microscopy (AFM) tip on graphite surface, AFM tip on C60/graphite, graphite on graphite surface, graphite/C60/graphite, and C60 intercalated graphite. For the atomic and flake frictions, frictional force maps are compared between simulations and experiments, which can be explained by stick-slip motion of the tip apex atom and flake. For the graphite/C60/graphite system, superlubricity appears, where the maximum static frictional forces have finite values but denote that dynamical frictional forces are zero within the resolution of the experiment. Furthermore, for the C60 intercalated graphite system, greater superlubricity appears. It is clarified that fullerene intercalated graphite films exhibit ultralow average friction force, and excellent friction coefficients μ < 0.001. Our results propose one of the simple guidelines of designing a practical superlubric system - reduction of the contact area between intercalated C60 and graphite sheet to the point contact. Clearly, the C60 intercalated graphite system will contribute to solving energy and environmental problems in the future.