Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues.

Abstract:

:The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Ku T,Swaney J,Park JY,Albanese A,Murray E,Cho JH,Park YG,Mangena V,Chen J,Chung K

doi

10.1038/nbt.3641

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

973-81

issue

9

eissn

1087-0156

issn

1546-1696

pii

nbt.3641

journal_volume

34

pub_type

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