Cell-based sensing platforms provide functional information on cellular effects of bioactive or toxic compounds in a sample. Current challenges concern the rather extended length of the assays as well as their limited reproducibility and sensitivity. We present a biosensing method capable of appraising, on a short time scale and with exquisite sensitivity, the occurrence and the magnitude of cellular alterations induced by low levels of a bioactive/toxic compound. Our method is based on integrating optogenetic control of non-electrogenic human cells, modified to express light sensitive protein channels, into a non-invasive electro-optical analytical platform enabling quantitative assessment of the stimulus dependent, dynamical cellular response. Our system exploits the interplay between optogenetic stimulation and time lapse fast impedance assays in boosting the platform sensitivity when exposing cells to a model exogenous stimulus, under both static and flow conditions. The proposed optogenetically modulated cell-based sensing platform is suitable for in field applications and provides a new paradigm for impedance-based sensing.
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http://dx.doi.org/10.1021/acs.analchem.9b03217 | DOI Listing |
Nature
January 2025
Laboratory of Protein Design and Immunoengineering, Institute of Bioengineering, Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland.
Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Science
January 2025
Department of Bioengineering, Rice University, Houston, TX, USA.
Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy in animal models. However, the mechanisms by which Spns1 transports lysophospholipid and proton sensing remain unclear.
View Article and Find Full Text PDFOncol Res
December 2024
Department of Biology, College of Science, Sultan Qaboos University, Muscat, 123, Oman.
Nanotechnology in cancer therapy has significantly advanced treatment precision, effectiveness, and safety, improving patient outcomes and personalized care. Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells, precisely sensing the tumor microenvironment (TME) and sparing normal cells. These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation, and they can also overcome therapy resistance and deliver multiple drugs simultaneously.
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