In nature, there exist a variety of transport proteins on cell membranes capable of actively moving cargos across biological membranes, which plays a vital role in the living activities of cells. Emulating such biological pumps in artificial systems may bring in-depth insights on the principles and functions of cell behaviors. However, it poses great challenges due to difficulty in the sophisticated construction of active channels at the cellular scale. Here, we report the development of bionic micropumps for active transmembrane transportation of molecular cargos across living cells that is realized by enzyme-powered microrobotic jets. By immobilizing urease onto the surface of a silica-based microtube, the prepared microjet is capable of catalyzing the decomposition of urea in surrounding environments and generating microfluidic flow through the inside channel for self-propulsion, which is verified by both numerical simulation and experimental results. Therefore, once naturally endocytosed by the cell, the microjet enables the diffusion and, more importantly, active transportation of molecular substances between the extracellular and intracellular ends with the assistance of generated microflow, thus serving as an artificial biomimetic micropump. Furthermore, by constructing enzymatic micropumps on cancer cell membranes, enhanced delivery of anticancer doxorubicin into cells as well as improved killing efficacy are achieved, which demonstrates the effectiveness of the active transmembrane drug transport strategy in cancer treatment. This work not only extends the applications of micro/nanomachines in biomedical fields but also provides a promising platform for future cell biology research at cellular and subcellular scales.
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http://dx.doi.org/10.1021/acsnano.3c00291 | DOI Listing |
Int J Mol Sci
January 2025
Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung Shan S. Rd. (Zhongshan S. Rd.), Zhongzheng Dist., Taipei City 100225, Taiwan.
Diabetic retinopathy (DR) is a complication of diabetes, characterized by progressive microvascular dysfunction that can result in vision loss. Chronic hyperglycemia drives oxidative stress, endothelial dysfunction, and inflammation, leading to retinal damage and complications such as neovascularization. Current treatments, including anti-VEGF agents, have limitations, necessitating the exploration of alternative therapeutic strategies.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Programa de Comunicación Celular en Cáncer, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7550000, Chile.
DUX4 is typically a repressed transcription factor, but its aberrant activation in Facioscapulohumeral Muscular Dystrophy (FSHD) leads to cell death by disrupting muscle homeostasis. This disruption affects crucial processes such as myogenesis, sarcolemma integrity, gene regulation, oxidative stress, immune response, and many other biological pathways. Notably, these disrupted processes have been associated, in other pathological contexts, with the presence of connexin (Cx) hemichannels-transmembrane structures that mediate communication between the intracellular and extracellular environments.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.
View Article and Find Full Text PDFCells
December 2024
Department of Breast Cancer Center, Samsung Medical Center, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, Republic of Korea.
Sushi domain-containing protein 2 (SUSD2), a transmembrane protein containing a sushi motif, has been reported to have tumor-promoting functions in various types of cancer, including breast cancer. However, the regulatory mechanism of SUSD2 and its function in HER2-positive (HER2+) breast cancer have not been fully identified as yet. In this study, we explored the potential of targeting SUSD2 to overcome trastuzumab (TRZ) resistance in HER2+ breast cancer.
View Article and Find Full Text PDFSkelet Muscle
January 2025
Department of Molecular Physiology and Biophysics, and Department of Neurology, Howard Hughes Medical Institute, Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Background: Maintaining the connection between skeletal muscle fibers and the surrounding basement membrane is essential for muscle function. Dystroglycan (DG) serves as a basement membrane extracellular matrix (ECM) receptor in many cells, and is also expressed in the outward-facing membrane, or sarcolemma, of skeletal muscle fibers. DG is a transmembrane protein comprised of two subunits: alpha-DG (α-DG), which resides in the peripheral membrane, and beta-DG (β-DG), which spans the membrane to intracellular regions.
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