Engineering the Cellular Microenvironment: Integrating Three-Dimensional Nontopographical and Two-Dimensional Biochemical Cues for Precise Control of Cellular Behavior.

The development of biomaterials capable of regulating cellular processes and guiding cell fate decisions has broad implications in tissue engineering, regenerative medicine, and cell-based assays for drug development and disease modeling. Recent studies have shown that three-dimensional (3D) nanoscale physical cues such as nanotopography can modulate various cellular processes like adhesion and endocytosis by inducing nanoscale curvature on the plasma and nuclear membranes. Two-dimensional (2D) biochemical cues such as protein micropatterns can also regulate cell function and fate by controlling cellular geometries. Development of biomaterials with precise control over nanoscale physical and biochemical cues can significantly influence programming cell function and fate. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate the precise engineering of single cell architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between the nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, our results suggest that cell elongation on nanopillars enhances nanopillar-induced endocytosis. We believe our platform serves as a versatile tool for further explorations into programming cell function and fate through combined physical cues that create nanoscale curvature on cell membranes and biochemical cues that control the geometry of the cell.

Amyloid-like nanofibrous network confined and aligned ultrafine bimetallic nanozymes for smart antibacterial therapy.

Nanozyme-based antibacterial therapy (NABT) has emerged as a promising strategy to combat bacterial antimicrobial resistance. Engineering the noble metal nanozymes with strong bacterial capture and high catalytic activity for enhanced NABT is highly anticipated but still challenged. Herein, we developed hybrid nanozymes by engineering ultrafine bimetallic Au/Cu nanoparticles confined on the lysozyme amyloid-like nanofibrous networks (LNF). The introduction of copper in the nanozymes facilitates the H2O2 adsorption and reduces the energy barrier for activating the H2O2 decomposition to form •OH, meanwhile displaying the significantly enhanced POD-like activity under NIR irradiation. Taking advantage of the inherent supramolecular networks inspired from human defensin 6-trapping bacteria mechanism, the hybrid nanozymes effectively capture the bacteria and allow the catalytic attack around the bacterial surfaces to improve the antibacterial efficiency. Finally, the as-prepared nanozymes exhibit the preeminent bactericidal efficacy against bacteria, especially for drug-resistant bacteria both in vitro and in vivo, and the effect on wound healing.