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1.
Nat Chem Biol ; 16(9): 988-996, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661379

RESUMO

Visualizing biomolecular and cellular processes inside intact living organisms is a major goal of chemical biology. However, existing molecular biosensors, based primarily on fluorescent emission, have limited utility in this context due to the scattering of light by tissue. In contrast, ultrasound can easily image deep tissue with high spatiotemporal resolution, but lacks the biosensors needed to connect its contrast to the activity of specific biomolecules such as enzymes. To overcome this limitation, we introduce the first genetically encodable acoustic biosensors-molecules that 'light up' in ultrasound imaging in response to protease activity. These biosensors are based on a unique class of air-filled protein nanostructures called gas vesicles, which we engineered to produce nonlinear ultrasound signals in response to the activity of three different protease enzymes. We demonstrate the ability of these biosensors to be imaged in vitro, inside engineered probiotic bacteria, and in vivo in the mouse gastrointestinal tract.


Assuntos
Acústica/instrumentação , Técnicas Biossensoriais/instrumentação , Enzimas/metabolismo , Trato Gastrointestinal/enzimologia , Ultrassonografia/métodos , Animais , Bactérias/enzimologia , Bactérias/genética , Técnicas Biossensoriais/métodos , Calpaína/análise , Calpaína/metabolismo , Endopeptidase Clp/genética , Endopeptidase Clp/metabolismo , Endopeptidases/análise , Endopeptidases/metabolismo , Enzimas/análise , Desenho de Equipamento , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Nanoestruturas/química , Potyvirus/enzimologia , Probióticos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Razão Sinal-Ruído , Ultrassonografia/instrumentação
2.
Nat Chem Biol ; 16(9): 1035, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32704181

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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