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1. Rationally designed chimeric solid‐binding peptides for tailoring solid interfaces

   https://doi.org/10.1002/mds3.10065  

   Yucesoy, Deniz T. ; Khatayevich, Dimitry ; Tamerler, Candan ; Sarikaya, Mehmet ( May 2020 , MEDICAL DEVICES & SENSORS)

   Joining biology with materials science requires the ability to design, engineer and control biology/solid‐state materials interfaces at the molecular level. The specific molecular interactions that take place among biomolecules, known as molecular recognition, enable all aspects of molecular processes in living systems prerequisite to the biological functions. Having the ability to establish specific biological interactions between the solid materials and biological constituents is essential for precise design of biologically viable soft interfaces that are molecularly tailored at solid surfaces. Solid‐binding peptides offer excellent opportunities in surface biofunctionalization over the traditionally utilized chemical approaches which generally make use of covalent bonds for surface molecular attachments with limited flexibility. Solid‐binding peptides are selected using directed evolution techniques using genotype to phenotype relationships and therefore referred also as genetically engineered peptides for inorganics (GEPI) and exclusively bind to solid materials using molecular recognition. Here, the peptide has weak interactions at multiple contact points that are established between the biomolecule and the solid lattice, and then folds into a conformation coherent with the underlying solid lattice through self‐organization on the surface. Solid‐binding peptides provide an unprecedented biological advantage as modular building blocks to couple biological and synthetic entities at the bio–solid interfaces. Taking full advantage of biology's versatility, they can easily be engineered to form chimeric molecules with inherent multifunctionality displaying biofunctional molecular entities, such as enzymes, co‐factors, antimicrobial peptides, antibodies, nucleic acids and molecular probes that target biomarkers. This minireview provides an insight into the key principles of solid‐binding peptides for advancing surfaces biofunctionalization by a selected set of examples on chimeric functions built upon linking, displaying and assembling functional molecular moieties at solid surfaces ranging from enzymatic biocatalysis to antimicrobial coatings. Modular multifunctional peptide design offers to tune molecular processes with coupled biological functions for a wide variety of applications in biotechnology, nanotechnology and medicine.

    

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2. On the interface of enzyme and spatial confinement: The impacts of confinement rigidity, shape, and surface properties on the interplay of enzyme structure, dynamics, and function

   https://doi.org/10.1063/5.0167117  

   Li, Qiaobin ; Armstrong, Zoe ; MacRae, Austin ; Lenertz, Mary ; Feng, Li ; Yang, Zhongyu ( December 2023 , Chemical Physics Reviews)

   Confining proteins in synthetic nanoscale spatial compartments has offered a cell-free avenue to understand enzyme structure–function relationships and complex cellular processes near the physiological conditions, an important branch of fundamental protein biophysics studies. Enzyme confinement has also provided advancement in biocatalysis by offering enhanced enzyme reusability, cost-efficiency, and substrate selectivity in certain cases for research and industrial applications. However, the primary research efforts in this area have been focused on the development of novel confinement materials and investigating protein adsorption/interaction with various surfaces, leaving a fundamental knowledge gap, namely, the lack of understanding of the confined enzymes (note that enzyme adsorption to or interactions with surfaces differs from enzyme confinement as the latter offers an enhanced extent of restriction to enzyme movement and/or conformational flexibility). In particular, there is limited understanding of enzymes' structure, dynamics, translocation (into biological pores), folding, and aggregation in extreme cases upon confinement, and how confinement properties such as the size, shape, and rigidity affect these details. The first barrier to bridge this gap is the difficulty in “penetrating” the “shielding” of the confinement walls experimentally; confinement could also lead to high heterogeneity and dynamics in the entrapped enzymes, challenging most protein-probing experimental techniques. The complexity is raised by the variety in the possible confinement environments that enzymes may encounter in nature or on lab benches, which can be categorized to rigid confinement with regular shapes, rigid restriction without regular shapes, and flexible/dynamic confinement which also introduces crowding effects. Thus, to bridge such a knowledge gap, it is critical to combine advanced materials and cutting-edge techniques to re-create the various confinement conditions and understand enzymes therein. We have spearheaded in this challenging area by creating various confinement conditions to restrict enzymes while exploring experimental techniques to understand enzyme behaviors upon confinement at the molecular/residue level. This review is to summarize our key findings on the molecular level details of enzymes confined in (i) rigid compartments with regular shapes based on pre-formed, mesoporous nanoparticles and Metal–Organic Frameworks/Covalent-Organic Frameworks (MOFs/COFs), (ii) rigid confinement with irregular crystal defects with shapes close to the outline of the confined enzymes via co-crystallization of enzymes with certain metal ions and ligands in the aqueous phase (biomineralization), and (iii) flexible, dynamic confinement created by protein-friendly polymeric materials and assemblies. Under each case, we will focus our discussion on (a) the way to load enzymes into the confined spaces, (b) the structural basis of the function and behavior of enzymes within each compartment environments, and (c) technical advances of our methodology to probe the needed structural information. The purposes are to depict the chemical physics details of enzymes at the challenging interface of natural molecules and synthetic compartment materials, guide the selection of enzyme confinement platforms for various applications, and generate excitement in the community on combining cutting-edge technologies and synthetic materials to better understand enzyme performance in biophysics, biocatalysis, and biomedical applications.

    

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3. Functionalizing DNA nanostructures for therapeutic applications

   https://doi.org/10.1002/wnan.1729  

   Henry, Skylar J. W. ; Stephanopoulos, Nicholas ( May 2021 , WIREs Nanomedicine and Nanobiotechnology)

   Recent advances in nanotechnology have enabled rapid progress in many areas of biomedical research, including drug delivery, targeted therapies, imaging, and sensing. The emerging field of DNA nanotechnology, in which oligonucleotides are designed to self‐assemble into programmable 2D and 3D nanostructures, offers great promise for further advancements in biomedicine. DNA nanostructures present highly addressable and functionally diverse platforms for biological applications due to their ease of construction, controllable architecture and size/shape, and multiple avenues for chemical modification. Both supramolecular and covalent modification with small molecules and polymers have been shown to expand or enhance the functions of DNA nanostructures in biological contexts. These alterations include the addition of small molecule, protein, or nucleic acid moieties that enable structural stability under physiological conditions, more efficient cellular uptake and targeting, delivery of various molecular cargos, stimulus‐responsive behaviors, or modulation of a host immune response. Herein, various types of DNA nanostructure modifications and their functional consequences are examined, followed by a brief discussion of the future opportunities for functionalized DNA nanostructures as well as the barriers that must be overcome before their translational use.

   This article is categorized under:

   Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

   Therapeutic Approaches and Drug Discovery > Emerging Technologies

   Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures

    

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4. The Diversity and Functions of Plant RNA Modifications: What We Know and Where We Go from Here

   https://doi.org/10.1146/annurev-arplant-071122-085813  

   Sharma, Bishwas ; Prall, Wil ; Bhatia, Garima ; Gregory, Brian D. ( May 2023 , Annual Review of Plant Biology)

   Since the discovery of the first ribonucleic acid (RNA) modifications in transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), scientists have been on a quest to decipher the identities and functions of RNA modifications in biological systems. The last decade has seen monumental growth in the number of studies that have characterized and assessed the functionalities of RNA modifications in the field of plant biology. Owing to these studies, we now categorize RNA modifications based on their chemical nature and the RNA on which they are found, as well as the array of proteins that are involved in the processes that add, read, and remove them from an RNA molecule. Beyond their identity, another key piece of the puzzle is the functional significance of the various types of RNA modifications. Here, we shed light on recent studies that help establish our current understanding of the diversity of RNA modifications found in plant transcriptomes and the functions they play at both the molecular (e.g., RNA stability, translation, and transport) and organismal (e.g., stress response and development) levels. Finally, we consider the key research questions related to plant gene expression and biology in general and highlight developments in various technologies that are driving our insights forward in this research area. 

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5. Mimicking Natural Photosynthesis: Designing Ultrafast Photosensitized Electron Transfer into Multiheme Cytochrome Protein Nanowires

   https://doi.org/10.3390/nano10112143  

   Marzolf, Daniel R. ; McKenzie, Aidan M. ; O’Malley, Matthew C. ; Ponomarenko, Nina S. ; Swaim, Coleman M. ; Brittain, Tyler J. ; Simmons, Natalie L. ; Pokkuluri, Phani Raj ; Mulfort, Karen L. ; Tiede, David M. ; et al ( November 2020 , Nanomaterials)

   null (Ed.)

   Efficient nanomaterials for artificial photosynthesis require fast and robust unidirectional electron transfer (ET) from photosensitizers through charge-separation and accumulation units to redox-active catalytic sites. We explored the ultrafast time-scale limits of photo-induced charge transfer between a Ru(II)tris(bipyridine) derivative photosensitizer and PpcA, a 3-heme c-type cytochrome serving as a nanoscale biological wire. Four covalent attachment sites (K28C, K29C, K52C, and G53C) were engineered in PpcA enabling site-specific covalent labeling with expected donor-acceptor (DA) distances of 4–8 Å. X-ray scattering results demonstrated that mutations and chemical labeling did not disrupt the structure of the proteins. Time-resolved spectroscopy revealed three orders of magnitude difference in charge transfer rates for the systems with otherwise similar DA distances and the same number of covalent bonds separating donors and acceptors. All-atom molecular dynamics simulations provided additional insight into the structure-function requirements for ultrafast charge transfer and the requirement of van der Waals contact between aromatic atoms of photosensitizers and hemes in order to observe sub-nanosecond ET. This work demonstrates opportunities to utilize multi-heme c-cytochromes as frameworks for designing ultrafast light-driven ET into charge-accumulating biohybrid model systems, and ultimately for mimicking the photosynthetic paradigm of efficiently coupling ultrafast, light-driven electron transfer chemistry to multi-step catalysis within small, experimentally versatile photosynthetic biohybrid assemblies. 

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