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Transient Photoinactivation of Cell Membrane Protein Activity without Genetic Modification by Molecular Hyperthermia
Univ Texas Dallas, Dept Mech Engn, 800 West Campbell Rd, Richardson, TX 75080 USA.
Univ Texas Dallas, Dept Bioengn, 800 West Campbell Rd, Richardson, TX 75080 USA.
Univ Texas Dallas, Dept Mech Engn, 800 West Campbell Rd, Richardson, TX 75080 USA.
Univ Texas Dallas, Sch Behav & Brain Sci, 800 West Campbell Rd, Richardson, TX 75080 USA.
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2019 (English)In: ACS Nano, ISSN 1936-0851, E-ISSN 1936-086X, Vol. 13, no 11, p. 12487-12499Article in journal (Refereed) Published
Abstract [en]

Precise manipulation of protein activity in living systems has broad applications in biomedical sciences. However, it is challenging to use light to manipulate protein activity in living systems without genetic modification. Here, we report a technique to optically switch off protein activity in living cells with high spatiotemporal resolution, referred to as molecular hyperthermia (MH). MH is based on the nanoscale-confined heating of plasmonic gold nanoparticles by short laser pulses to unfold and photoinactivate targeted proteins of interest. First, we show that protease-activated receptor 2 (PAR2), a G-protein-coupled receptor and an important pathway that leads to pain sensitization, can be photoinactivated in situ by MH without compromising cell proliferation. PAR2 activity can be switched off in laser-targeted cells without affecting surrounding cells. Furthermore, we demonstrate the molecular specificity of MH by inactivating PAR2 while leaving other receptors intact. Second, we demonstrate that the photoinactivation of a tight junction protein in brain endothelial monolayers leads to a reversible blood-brain barrier opening in vitro. Lastly, the protein inactivation by MH is below the nanobubble generation threshold and thus is predominantly due to the nanoscale heating. MH is distinct from traditional hyperthermia (that induces global tissue heating) in both its time and length scales: nanoseconds versus seconds, nanometers versus millimeters. Our results demonstrate that MH enables selective and remote manipulation of protein activity and cellular behavior without genetic modification.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2019. Vol. 13, no 11, p. 12487-12499
Keywords [en]
plasmonic nanoparticle, nanosecond laser, protein inactivation, G-protein-coupled receptor, blood-brain barrier
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-400680DOI: 10.1021/acsnano.9b01993ISI: 000500650000025PubMedID: 31613606OAI: oai:DiVA.org:uu-400680DiVA, id: diva2:1382180
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

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Dejana, Elisabetta

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