The contributions of model studies for fundamental understanding of polymer mechanochemistry

The exciting field of polymer mechanochemistry has made great empirical progress in discovering reactions in which a stretching force accelerates scission of strained bonds using single molecule force spectroscopy and ultra-sonication experiments. Understanding why these reactions happen, i.e., the fundamental physical processes that govern coupling of macroscopic motion to chemical reactions, as well as discovering other patterns of mechanochemical reactivity require complementary techniques, which permit a much more detailed characterization of reaction mechanisms and the distribution of force in reacting molecules than are achievable in SMFS or ultrasonication. A molecular force probe allows the specific pattern of molecular strain that is responsible for localized reactions in stretched polymers to be reproduced accurately in non-polymeric substrates using molecular design rather than atomistically intractable collective motions of millions of atoms comprising macroscopic motion. In this review, we highlight the necessary features of a useful molecular force probe and describe their realization in stiff stilbene macrocycles. We describe how studying these macrocycles using classical tools of physical organic chemistry has allowed detailed characterizations of mechanochemical reactivity, explain some of the most unexpected insights enabled by these probes and speculate how they may guide the next stage of mechanochemistry.

Obtaining Precise Molecular Information via DNA Nanotechnology

Precise characterization of biomolecular information such as molecular structures or intermolecular interactions provides essential mechanistic insights into the understanding of biochemical processes. As the resolution of imaging-based measurement techniques improves, so does the quantity of molecular information obtained using these methodologies. DNA (deoxyribonucleic acid) molecule have been used to build a variety of structures and dynamic devices on the nanoscale over the past 20 years, which has provided an accessible platform to manipulate molecules and resolve molecular information with unprecedented precision. In this review, we summarize recent progress related to obtaining precise molecular information using DNA nanotechnology. After a brief introduction to the development and features of structural and dynamic DNA nanotechnology, we outline some of the promising applications of DNA nanotechnology in structural biochemistry and in molecular biophysics. In particular, we highlight the use of DNA nanotechnology in determination of protein structures, protein–protein interactions, and molecular force.

Turn-key mapping of cell receptor force orientation and magnitude using a commercial structured illumination microscope

Many cellular processes, including cell division, development, and cell migration require spatially and temporally coordinated forces transduced by cell-surface receptors. Nucleic acid-based molecular tension probes allow one to visualize the piconewton (pN) forces applied by these receptors. Building on this technology, we recently developed molecular force microscopy (MFM) which uses fluorescence polarization to map receptor force orientation with diffraction-limited resolution (~250 nm). Here, we show that structured illumination microscopy (SIM), a super-resolution technique, can be used to perform super-resolution MFM. Using SIM-MFM, we generate the highest resolution maps of both the magnitude and orientation of the pN traction forces applied by cells. We apply SIM-MFM to map platelet and fibroblast integrin forces, as well as T cell receptor forces. Using SIM-MFM, we show that platelet traction force alignment occurs on a longer timescale than adhesion. Importantly, SIM-MFM can be implemented on any standard SIM microscope without hardware modifications.

Quantification of fast molecular adhesion by fluorescence footprinting

Rolling adhesion is a unique process in which the adhesion events are short-lived and operate under highly nonequilibrium conditions. These characteristics pose a challenge in molecular force quantification, where in situ measurement of these forces cannot be achieved with molecular force sensors that probe near equilibrium. Here, we demonstrated a quantitative adhesion footprint assay combining DNA-based nonequilibrium force probes and modeling to measure the molecular force involved in fast rolling adhesion. We were able to directly profile the ensemble molecular force distribution in our system during rolling adhesion with a dynamic range between 0 and 18 pN. Our results showed that the shear stress driving bead rolling motility directly controls the molecular tension on the probe-conjugated adhesion complex. Furthermore, the shear stress can steer the dissociation bias of components within the molecular force probe complex, favoring either DNA probe dissociation or receptor-ligand dissociation.

Overview of Molecular Dynamics Simulation of Natural Gas Hydrate at Nanoscale

As a dynamic research method for molecular systems, molecular dynamic (MD) simulation can represent physical phenomena that cannot be realized by experimental means and discuss the microscopic reaction mechanism of things from the molecular level. In this paper, the previous research results were reviewed. First, the MD simulation process was briefly described, then, the applicability of different molecular force fields in the natural gas hydrate (NGH) system was discussed, and finally, the application of MD simulation in the formation and decomposition law of NGH was summarized from the perspective of NGH mining. The results show that the selection of water molecular force field has a great influence on the simulation results, and the evaluation of water model applicable to the simulation of NGH under different thermodynamic states is still an open research field that needs to be paid attention to. The effect of surface properties of porous media (such as crystallinity and hydrophilicity) on hydrate needs to be further studied. Compared with thermodynamic inhibitors, kinetic inhibitors (such as amino acids) have more promising research prospects, and further research can be carried out in the screening of efficient kinetic inhibitors in the future.