Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell–Cell Interactions

Abstract

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell–cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell–cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. This study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.

Photofabrication of fluorescent nanospheres from de novo designed peptides, and their enzyme-responsive dissociation in living cells

“…13–16 Peptide assemblies are ordinarily governed by a combination of noncovalent and covalent interactions, encompassing hydrogen bonds, 17 π–π stacking, 18 hydrophobic interactions, 19,20 coulombic forces, 21,22 disulfide S–S bonds, 23,24 l -phenylalanine polymerization, dityrosine crosslinking, 25–27 and so on, which could drive peptide self-assembly processes, stabilize secondary or tertiary structures, and establish conjugation patterns even at the protein level. Tremendous efforts have been made to exploit de novo designed peptides and mimic bioactive assemblies, however, the function-oriented synthesis is still limited by many influencing factors of pH environment, 28–30 working temperature, 31–33 ionic strength, 34,35 hydrophilic/hydrophobic properties, 36,37 pre-assembly method, 38,39 host–guest modeling, 40,41 spacer occupation, 42,43 and so on.…”

Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by Enhancing Blood Shear Stress Adaptation

“…Since cells themselves are the basic units of living creatures, appropriately selected and engineered cells are highly biocompatible. , Furthermore, as functional units, living cells could accomplish multiple and otherwise difficult tasks in vivo such as targeted movement, biological barrier penetration, and highly specific cell killing . In fact, living cells have already been widely used for personalized medicine in clinics, with several highly successful applications, such as the chimeric antigen receptor T cells (CAR-T) engineered for leukemia treatment. − When being used as drug carriers, the characteristics of cells may be exploited to achieve significantly improved therapeutic efficiency and biosafety. − Cancer is a major research topic in drug delivery systems, and one of the most widely used cell vehicles for cancer treatment is a macrophage, and the release of cytokines by tumor cells under hypoxia attracts macrophages. − …”

“…Unfortunately, blood FSS is often overlooked when designing live cell delivery systems; therefore, many cell vehicles are limited due to the negative effects of FSS. − , Due to the role of ROS in the cellular FSS response, strengthening ROS resistance in cell vehicles may be beneficial. Although small-molecule ROS inhibitors and nanozymes could achieve anti-ROS effects, − adding these agents to delivery systems increases system complexity and may bring unwanted side effects that hinder clinical translation. ,, Surface modification, such as adding PEG to the cell surface, may also reduce the impact of FSS-induced ROS; however, the modification process may affect cell viability and the added layer may disturb the motility of cells . Therefore, a simple and mild engineering strategy to enhance the resistance of cell vehicles to FSS-induced ROS would be valuable.…”