The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Here we describe a molecular system that can be programmed to control these three characteristics. In this approach we immobilize peptide-DNA (P-DNA) molecules on a surface through complementary DNA tethers directing cells to adhere and spread reversibly over multiple cycles. The DNA can also serve as a molecular ruler to control the distance-dependent synergy between two peptides. Finally, we use two orthogonal DNA handles to regulate two different bioactive signals, with the ability to independently up- or downregulate each over time. This enabled us to discover that neural stem cells, derived from the murine spinal cord and organized as neurospheres, can be triggered to migrate out in response to an exogenous signal but then regroup into a neurosphere as the signal is removed.
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http://dx.doi.org/10.1038/ncomms15982 | DOI Listing |
Nat Immunol
January 2025
Department of Immunology and Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT, USA.
T cells recognize neoepitope peptide-major histocompatibility complex class I on cancer cells. The strength (or avidity) of the T cell receptor-peptide-major histocompatibility complex class I interaction is a critical variable in immune control of cancers. Here, we analyze neoepitope-specific CD8 cells of distinct avidities and show that low-avidity T cells are the sole mediators of cancer control in mice and are solely responsive to checkpoint blockade in mice and humans.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Acinetobacter baumannii, an opportunistic bacterium prevalent in various environment, is a significant cause of nosocomial infections in ICUs. As the causative agent of pneumonia, septicemia, and meningitis, A. baumannii typically exhibits multidrug resistance and is associated with poor prognosis, thus led to a challenge for researchers in developing new treatment and prevention methods.
View Article and Find Full Text PDFACS Biomater Sci Eng
January 2025
Weldon School of Biomedical Engineering, Purdue University, West Lafayette 47907-2050, Indiana, United States.
Granular hydrogels are injectable and inherently porous biomaterials assembled through the packing of microparticles. These particles typically have a symmetric and spherical shape. However, recent studies have shown that asymmetric particles with high aspect ratios, such as fibers and rods, can significantly improve the mechanics, structure, and cell-guidance ability of granular hydrogels.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
January 2025
Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
The in vitro blood-brain barrier (BBB) structures can offer advantages for studying cerebrovascular functions and developing neuroprotective drugs. However, currently developed BBB models are overly simplistic and inadequate for replicating the complex three-dimensional architecture of the in vivo BBB. In this study, a method is introduced for fabricating a three-layer vascular structure exhibiting BBB function using a coaxial extrusion bioprinting technique with a two-layer nozzle.
View Article and Find Full Text PDFClin Cancer Res
January 2025
University of Leeds, Leeds, United Kingdom.
Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.
Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.
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