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Structural and molecular interrogation of intact biological systems.

ABSTRACT: Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.

SUBMITTER: Chung K

PROVIDER: S-EPMC4092167 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Structural and molecular interrogation of intact biological systems.

Chung Kwanghun K Wallace Jenelle J Kim Sung-Yon SY Kalyanasundaram Sandhiya S Andalman Aaron S AS Davidson Thomas J TJ Mirzabekov Julie J JJ Zalocusky Kelly A KA Mattis Joanna J Denisin Aleksandra K AK Pak Sally S Bernstein Hannah H Ramakrishnan Charu C Grosenick Logan L Gradinaru Viviana V Deisseroth Karl K

Nature 20130410 7449

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show ...[more]

PMID: 23575631

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Structural and molecular interrogation of intact biological systems.

Publications

Structural and molecular interrogation of intact biological systems.

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