Cell Surface Engineering Tools for Programming Living Assemblies

Abstract

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.

Surface Engineering of Natural Killer Cells with CD44‐targeting Ligands for Augmented Cancer Immunotherapy

“…The distinctive characteristic of the lipid anchor, allowing for immediate and consistent surface modification, sets it apart from previously developed cell surface engineering techniques established over the past few decades, many of which are often associated with significant limitations. [ 34 ] For instance, genetic engineering has the potential to induce mutagenesis and tumorigenesis. In addition, glycoengineering demands ≈48 h for the expression of the target molecules, with the expression pattern of the ligand relying entirely on the unpredictable metabolic processes of the cell.…”

Bacterial Patterning: A Promising Biofabrication Technique

“…15−17 Despite extensive discussions on biomolecular patterning, 18 mammalian cell patterning, 19,20 and 3D printing, 21,22 there is a lack of prior publications systematically summarizing the research progress of bacterial patterning for diverse applications. In contrast to fragile mammalian cells, which are susceptible to environmental stimulation, 23,24 bacterial cells possess an additional cell wall structure, which serves as a protective shell to defend against external influential factors (e.g., shear force and light irradiation). 25,26 Moreover, bacterial cells can form self-embedded biofilms by secreting extracellular polymeric substances (EPSs; e.g., polysaccharides, proteins, and extracellular DNAs) and adhering to surfaces, which provide protection to bacteria in harsh environments.…”

“… − At the microscopic scale, precise micro- and nanoscopic patterns are created through the deposition and/or adhesion of single molecules, exemplified by protein arrays for investigating signaling pathways and ligand–receptor interactions. − On the macroscopic scale, three-dimensional (3D) printing is employed to generate multicellular assemblies with precise geometries for mimicking the biological functions of native tissues and organs. − Despite extensive discussions on biomolecular patterning, mammalian cell patterning, , and 3D printing, , there is a lack of prior publications systematically summarizing the research progress of bacterial patterning for diverse applications. In contrast to fragile mammalian cells, which are susceptible to environmental stimulation, , bacterial cells possess an additional cell wall structure, which serves as a protective shell to defend against external influential factors (e.g., shear force and light irradiation). , Moreover, bacterial cells can form self-embedded biofilms by secreting extracellular polymeric substances (EPSs; e.g., polysaccharides, proteins, and extracellular DNAs) and adhering to surfaces, which provide protection to bacteria in harsh environments. , Given their rapid proliferation, strong colonization capability, environmental adaptability, and well-established gene manipulation strategies, bacterial cells are considered ideal candidates for biopatterning. − …”

Investigation on Adaptability and Applicability of Polymer-Mediated Cell Surface Engineering by Ligation with Transglutaminase

“…There is a range of techniques available for modifying the cell surface, but the selection of the most suitable technique depends on factors such as cell type, application, and handling requirements. ,, The modification of cell surfaces without toxic effects is a powerful engineering strategy to manipulate cell behavior for specific biomedical applications . Cell surface modification techniques need to be biorthogonal, compatible with the cell environment, and not generate toxic byproducts.…”