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Biological hydrogen production by microbial cells has been extensively researched as an energy-efficient and environmentally-friendly process. In this study, we propose a fast, easy method for immobilizing Enterobacter aerogenes by expressing ataA, which encodes the adhesive protein of Acinetobacter sp. Tol 5. AtaA protein on the E. aerogenes cells carrying the ataA gene was demonstrated by immunoblotting and flow cytometry. The AtaA-producing cells exhibited stronger adherence and auto-agglutination characteristics than wild-type cells, and were successfully immobilized (at approximately 2.5 mg/cm3) on polyurethane foam. Hydrogen production from the cell-immobilized polyurethane foams was monitored in repetitive batch reactions and flow reactor studies. The total hydrogen production in triple-repetitive batch reactions reached 0.6 mol/mol glucose, and the hydrogen production rate in the flow reactor was 42 mL·h−1·L−1. The AtaA production achieved simple and immediate immobilization of E. aerogenes on the foam, enabling repetitive and continuous hydrogen production. This report newly demonstrates the production of AtaA on the cell surfaces of bacterial genera other than Acinetobacter, and can simplify and accelerate the immobilization of whole-cell catalysts.

Uranium is one of the most important metal resources, and the technology for the recovery of uranyl ions (UO22+) from aqueous solutions is required to ensure a semi-permanent supply of uranium. The NikR protein is a Ni2+-dependent transcriptional repressor of the nickel-ion uptake system in Escherichia coli, but its mutant protein (NikRm) is able to selectively bind uranyl ions in the interface of the two monomers. In this study, NikRm protein with ability to adsorb uranyl ions was displayed on the cell surface of Saccharomyces cerevisiae. To perform the binding of metal ions in the interface of the two monomers, two metal-binding domains (MBDs) of NikRm were tandemly fused via linker peptides and displayed on the yeast cell surface by fusion with the cell wall-anchoring domain of yeast α-agglutinin. The NikRm-MBD-displaying yeast cells with particular linker lengths showed the enhanced adsorption of uranyl ions in comparison to the control strain. By treating cells with citrate buffer (pH 4.3), the uranyl ions adsorbed on the cell surface were recovered. Our results indicate that the adsorption system by yeast cells displaying tandemly fused MBDs of NikRm is effective for simple and concentrated recovery of uranyl ions, as well as adsorption of uranyl ions.

Breakthroughs in precision cell surface engineering tools are supporting the rapid development of programmable living assemblies with valuable features for tackling complex biological problems. Herein, the authors overview the most recent technological advances in chemically‐ and biologically‐driven toolboxes for engineering mammalian cell surfaces and triggering their assembly into living architectures. A particular focus is given to surface engineering technologies for enabling biomimetic cell–cell social interactions and multicellular cell‐sorting events. Further advancements in cell surface modification technologies may expand the currently available bioengineering toolset and unlock a new generation of personalized cell therapeutics with clinically relevant biofunctionalities. The combination of state‐of‐the‐art cell surface modifications with advanced biofabrication technologies is envisioned to contribute toward generating living materials with increasing tissue/organ‐mimetic bioactivities and therapeutic potential. Cell surface engineering can be explored for generating multicellular living assemblies with user‐defined designs and biological programmability. This review provides a comprehensive overview of currently available toolboxes, as well as presents a critical discussion on the most recent advances and exploitable paths to open potential applications of surface functionalized cells in biotechnology and healthcare.

The encapsulation of cells with various polyelectrolytes through layer-by-layer (LbL) has become a popular strategy in cellular function engineering. The technique sprang up in 1990s and obtained tremendous advances in multi-functionalized encapsulation of cells in recent years. This review comprehensively summarized the basis and applications in drug delivery by means of LbL cell encapsulation. To begin with, the concept and brief history of LbL and LbL cell encapsulation were introduced. Next, diverse types of materials, including naturally extracted and chemically synthesized, were exhibited, followed by a complicated basis of LbL assembly, such as interactions within multilayers, charge distribution, and films morphology. Furthermore, the review focused on the protective effects against adverse factors, and bioactive payloads incorporation could be realized via LbL cell encapsulation. Additionally, the payload delivery from cell encapsulation system could be adjusted by environment, redox, biological processes, and functional linkers to release payloads in controlled manners. In short, drug delivery via LbL cell encapsulation, which takes advantage of both cell grafts and drug activities, will be of great importance in basic research of cell science and biotherapy for various diseases.

Red blood cells (RBCs) are the most abundant cell type in the blood, and play a critical role in oxygen transport. With the development of nanobiotechnology and synthetic biology, scientists have found multiple ways to take advantage of the characteristics of RBCs, such as their long circulation time, to construct universal RBCs, develop drug delivery systems, and transform cell therapies for cancer and other diseases. This article reviews the component and aging mystery of RBCs, the methods for the applied universal RBCs, and the application prospects of RBCs, such as the engineering modification of RBCs used in cytopharmaceuticals for drug delivery and immunotherapy. Finally, we summarize some perspectives on the biological features of RBCs and provide further insights into translational medicine.

In pathological bone conditions (e.g., osteoporotic fractures or critical size bone defects), increasing the pool of osteoblast progenitor cells is a promising therapeutic approach to facilitate bone healing. Since mesenchymal stem cells (MSCs) give rise to the osteogenic lineage, a number of clinical trials investigated the potential of MSCs transplantation for bone regeneration. However, the engraftment of transplanted cells is often hindered by insufficient oxygen and nutrients supply and the tendency of MSCs to home to different sites of the body. In this review, we discuss various approaches of MSCs transplantation for bone regeneration including scaffold and hydrogel constructs, genetic modifications and surface engineering of the cell membrane aimed to improve homing and increase cell viability, proliferation and differentiation.

Cell-based therapy has expanded its influence in cancer immunotherapy, regenerative medicine, and tissue engineering. Due to their secretory functions, differentiation capabilities, specific homing effects through chemotaxis, distinctive therapeutic potentials, and ex vivo expandability, cells have become an attractive reagent for advanced therapeutic strategies. Therefore, the ability to modify cells and manipulate their functions according to intended therapeutic designs has been the central scientific interest in the field of biomedical research. Many innovative methods have been developed with genetic modification of cells being the most advanced cell surface engineering technique. Although genetic modification is a powerful tool, it has a limited applicability due to the permanent modifications made on cells. Alternatively, many endeavors have been made to develop surface engineering techniques that can circumvent the limitations of genetic modification. In this review, current methods of non-genetic cell surface modification, including chemical conjugations, polymeric encapsulation, hydrophobic insertion, enzymatic and metabolic addition, will be introduced. Moreover, cell surface engineering plausible for cardiac remodeling and the future prospective will be discussed at the end.

Protein display approaches have been useful to endow the cell surface of yeasts with new catalytic activities so that they can act as enhanced whole-cell biocatalysts. Despite their biotechnological potential, protein display technologies remain poorly developed for filamentous fungi. The lignocellulolytic character of some of them coupled to the cell surface biosynthesis of valuable molecules by a single or a cascade of several displayed enzymes is an appealing prospect. Cell surface protein display consists in the co-translational fusion of a functional protein (passenger) to an anchor one, usually a cell-wall–resident protein. The abundance, spacing, and local environment of the displayed enzymes—determined by the relationship of the anchor protein with the structure and dynamics of the engineered cell wall—are factors that influence the performance of display-based biocatalysts. The development of protein display strategies in filamentous fungi could be based on the field advances in yeasts; however, the unique composition, structure, and biology of filamentous fungi cell walls require the customization of the approach to those microorganisms. In this prospective review, the cellular bases, the design principles, and the available tools to foster the development of cell surface protein display technologies in filamentous fungi are discussed.

Organoids are three‐dimensional (3D) cell culture systems that simulate the structures and functions of organs, involving applications in disease modeling, drug screening, and cellular developmental biology. The material matrix in organoids can provide a 3D environment for stem cells to differentiate into different cell types and continuously self‐renew, thereby realizing the in vitro culture of organs, which has received extensive attention in recent years. However, some challenges still exist in organoids, including low maturity, high heterogeneity, and lack of spatiotemporal regulation. Therefore, in this review, we summarized the culturing protocols and various applications of stem cell‐derived organoids and proposed insightful thoughts for engineering stem cells into organoids in view of the current shortcomings, to achieve the further application and clinical translation of stem cells and engineered stem cells in organoid research. In this review, we summarized the culturing protocols and various applications of stem cell‐derived organoids and proposed insightful thoughts for engineering stem cells into organoids in view of the current shortcomings, to achieve the further application and clinical translation of stem cells and engineered stem cells in organoid research.

Metastasis is a leading cause of mortality in breast cancer and is critically influenced by cell–extracellular matrix (ECM) interactions, mechanical forces, and cellular motility. In this study, we present a cell surface engineering approach using tris(2-carboxyethyl)phosphine (TCEP), a biocompatible thiol-modifying agent, to modulate the biomechanical behavior of breast cancer cells. TCEP treatment increased surface thiol availability, enhanced phosphorylation of focal adhesion kinase (FAK), and promoted the elongation of pFAK-positive focal adhesions, along with cytoskeletal remodeling and stronger cell–ECM adhesion. These molecular and structural changes corresponded with significantly reduced migration and invasion of MCF7 and MDA-MB-231 cells. Using traction force microscopy (TFM), we further observed increased intracellular tension and traction stress, providing quantitative insight into how surface modification regulates mechanotransduction. These findings highlight the potential of cell surface thiol engineering to control cancer cell adhesion and motility, providing a platform for future identification of clinically applicable redox-modulating agents. Graphical abstract TCEP-mediated surface thiol modulation enhances focal adhesion and mechanical force generation, thereby suppressing breast cancer cell migration and invasion. Treatment with the biocompatible reducing agent TCEP cleaves cell surface disulfide bonds, increasing free thiol groups and reinforcing focal adhesion structures via FAK phosphorylation and actin remodeling. This redox modulation elevates traction force and intracellular stress, ultimately impairing both single-cell and collective migration. These findings identify surface thiol redox balance as a critical regulator of adhesion dynamics and mechanotransduction in breast cancer cells.