ABSTRACT
Peptide coacervates self-assembling via liquid-liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non-cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, identify the key steps by which droplets enter the cell. find that the uptake follows a non-canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia-like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge- and cholesterol-dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors - interfering with actin and tubulin polymerization - confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non-specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate-based strategies for intracellular delivery of macromolecular therapeutics.
ABSTRACT
Chemical sensors allow for continuous detection and analysis of underexplored molecules in the human body and the surroundings and have promising applications in human healthcare and environmental protection. With the increasing number of chemical sensors and their wide-range distribution, developing a continuous, sustainable, and pervasive power supply is vitally important but an unmet scientific challenge to perform chemical sensing. Self-powered chemical sensing via triboelectric nanogenerators (TENGs) could be a promising approach to this critical situation. TENGs can convert mechanical triggers from the surroundings into usable electrical signals for chemical sensing in a self-powered and environment-friendly manner. Moreover, their simple structure, low probability of failure, and wide choice of materials distinguish them from other chemical sensing technologies. This review article discusses the working principles of TENGs and their applications in chemical sensing with respect to the role of TENGs as either a self-powered sensor or a power source for existing chemical sensors. Advances in materials innovation and nanotechnology to optimize the chemical sensing performances are discussed and emphasized. Finally, the current challenges and future prospect of TENG enabled self-powered chemical sensing are discussed to promote interdisciplinary field development and revolutions.
ABSTRACT
Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 µM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.