A Life of Biophysics

Biophysics is a way of approaching biological problems through numbers, physical laws, models, and quantitative logic. In a long scientific career, I have seen the formation and fruition of the ion channel concept through biophysical study. Marvelous discoveries were made as our instruments evolved from vacuum tubes to transistors; computers evolved from the size of an entire building to a few chips inside our instruments; and genome sequencing, gene expression, and atom-level structural biology became accessible to all laboratories. Science is rewarding and exhilarating. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

1H NMR Elucidation of Observed Stable Sugar-NaCl-water Complexes in Aqueous Solution

The solvation of sugars in aqueous media matters in the understanding of biological systems and carbohydrate transformations. Generally, 2 – 4 water units were proposed to interact with each hydroxyl group in monosaccharides via different types of hydrogen bondings at room temperature in previous studies. Presence of NaCl was known to perturb hydrogen bondings of sugar hydrates. However, direct evidence to elucidate mechanism at atom level is very rare even though “NaCl Effect” was well known in biomass chemical transformations. Here we report 1H NMR elucidation evidences of mono/disaccharides hydrates in different concentration of NaCl aqueous solutions. We here conclude two new findings: 1) under ideal usage of NaCl, different mono/disaccharides hydrates are likely to be converted into a stable sugar-NaCl-water form; 2) pKa value of different hydroxyls in mono/disaccharides has intangible influence on hydrate form change induced by NaCl. An ideal NaCl usage based on maximum of 1H NMR shift was proposed.

Hierarchical Harmonization of Atom-Resolved Metabolic Reactions across Metabolic Databases

Metabolic models have been proven to be useful tools in system biology and have been successfully applied to various research fields in a wide range of organisms. A relatively complete metabolic network is a prerequisite for deriving reliable metabolic models. The first step in constructing metabolic network is to harmonize compounds and reactions across different metabolic databases. However, effectively integrating data from various sources still remains a big challenge. Incomplete and inconsistent atomistic details in compound representations across databases is a very important limiting factor. Here, we optimized a subgraph isomorphism detection algorithm to validate generic compound pairs. Moreover, we defined a set of harmonization relationship types between compounds to deal with inconsistent chemical details while successfully capturing atom-level characteristics, enabling a more complete enabling compound harmonization across metabolic databases. In total, 15,704 compound pairs across KEGG (Kyoto Encyclopedia of Genes and Genomes) and MetaCyc databases were detected. Furthermore, utilizing the classification of compound pairs and EC (Enzyme Commission) numbers of reactions, we established hierarchical relationships between metabolic reactions, enabling the harmonization of 3856 reaction pairs. In addition, we created and used atom-specific identifiers to evaluate the consistency of atom mappings within and between harmonized reactions, detecting some consistency issues between the reaction and compound descriptions in these metabolic databases.

Hierarchical Harmonization of Atom-Resolved Metabolic Re-actions Across Metabolic Databases

Metabolic models have been proven to be useful tools in system biology and have been suc-cessfully applied to various research fields in a wide range of organisms. A relatively complete metabolic network is a prerequisite for deriving reliable metabolic models. The first step in con-structing metabolic network is to harmonize compounds and reactions across different metabolic databases. However, effectively integrating data from various sources still remains a big chal-lenge. Incomplete and inconsistent atomistic details in compound representations across data-bases is a very important limiting factor. Here, we optimized a subgraph isomorphism detection algorithm to validate generic compound pairs. Moreover, we defined a set of harmonization re-lationship types between compounds to deal with inconsistent chemical details while successfully capturing atom-level characteristics, enabling a more complete enabling compound harmoniza-tion across metabolic databases. In total, 15,704 compound pairs across KEGG (Kyoto Encyclo-pedia of Genes and Genomes) and MetaCyc databases were detected. Furthermore, utilizing the classification of compound pairs and EC (Enzyme Commission) numbers of reactions, we estab-lished hierarchical relationships between metabolic reactions, enabling the harmonization of 3,856 reaction pairs. In addition, we created and used atom-specific identifiers to evaluate the con-sistency of atom mappings within and between harmonized reactions, detecting some con-sistency issues between the reaction and compound descriptions in these metabolic databases.

A Mechanically Reprogrammable Pancharatnam-Berry Metasurface

Metasurfaces have enabled the realization of several optical functionalities over an ultrathin platform, fostering the exciting field of flat optics. Traditional metasurfaces are achieved by arranging a layout of static meta-atoms to imprint a desired operation to the impinging wavefront, but their functionality cannot be altered. Reconfigurability and programmability of metasurfaces are the next important step to broaden their impact, adding customized on-demand functionality in which each meta-atom can be individually reprogrammed. However, programmable metasurfaces to date can only reconfigure 2 or 4 phase levels per meta-atom at best, hindering the overall functionality performance. Here, we demonstrate a mechanical metasurface platform with controllable rotation at the meta-atom level, which can implement continuous Pancharatnam-Berry phase control of circularly polarized waves. As the proof-of-concept experiments, we demonstrate metalensing, focused vortex beam generation, and holographic imaging in the same metasurface template, exhibiting versatility and superior performance. Such dynamic control of electromagnetic waves using a single, low-cost metasurface paves an avenue towards practical applications, driving the field of reprogrammable intelligent metasurfaces for a variety of applications.

Single-atom level determination of 3-dimensional surface atomic structure via neural network-assisted atomic electron tomography

Functional properties of nanomaterials strongly depend on their surface atomic structures, but they often become largely different from their bulk structures, exhibiting surface reconstructions and relaxations. However, most of the surface characterization methods are either limited to 2D measurements or not reaching to true 3D atomic-scale resolution, and single-atom level determination of the 3D surface atomic structure for general 3D nanomaterials still remains elusive. Here we demonstrate the measurement of 3D atomic structure at 15 pm precision using a Pt nanoparticle as a model system. Aided by a deep learning-based missing data retrieval combined with atomic electron tomography, the surface atomic structure was reliably measured. We found that <$$100$$ 100 > and <$$111$$ 111 > facets contribute differently to the surface strain, resulting in anisotropic strain distribution as well as compressive support boundary effect. The capability of single-atom level surface characterization will not only deepen our understanding of the functional properties of nanomaterials but also open a new door for fine tailoring of their performance.