What Is Spatial Proteomics?
- Cancer microenvironment: Interactions between tumor cells and immune cells frequently occur in specific regions, such as the tumor margin or core.
- Nervous system: Neurotransmitter receptors and related proteins exhibit distinct regional distribution patterns.
- Drug targets: The same protein may exert completely different biological functions depending on its localization in different tissues or subcellular compartments.
- Their localization in subcellular structures (nucleus, mitochondria, plasma membrane, etc)
- Their spatial positions within tissue sections
- Expression differences among distinct spatial regions
- MIBI (Multiplexed Ion Beam Imaging)
- IMC (Imaging Mass Cytometry)
- CODEX (Co-detection by indexing)
- Protein analysis of tumor subregions
- High-precision proteomics for specific tissue structures (e.g., neurons, glomeruli)
- Drug-target validation and mechanism studies
Spatial proteomics integrates proteomic analysis with spatial localization technologies to characterize the distribution, abundance, and interactions of proteins at the tissue, cellular, and even subcellular levels. This field centers on three key questions: where proteins reside, with which partners they interact, and how their functions vary across locations. Traditional proteomic workflows typically require homogenization of biological samples to generate bulk protein expression profiles. Although this averaged approach is useful for large-scale screening, it eliminates essential information regarding the spatial organization of proteins within tissues or cells. Spatial proteomics emerged to overcome this limitation, preserving structural context and providing an additional spatial dimension for studying biological processes, disease mechanisms, and drug actions.
Why Is Spatial Information Important?
Biological processes do not take place in homogeneous environments. Several examples highlight the relevance of spatial localization:
Core Concepts of Spatial Proteomics
Spatial proteomics aims to interpret protein function within the structural framework of tissues or cellular environments. Thus, researchers seek not only to identify proteins and quantify their abundances but also to determine:
Technical Approaches in Spatial Proteomics
Spatial proteomics combines mass spectrometry with microscopy-based imaging. Common strategies include:
1. Mass Spectrometry Imaging (MSI)
This label-free technique scans tissue sections using mass spectrometry to generate spatial distribution maps of proteins, metabolites, or lipids. Representative MSI approaches include:
(1) MALDI-MSI (Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging)
(2) DESI-MSI (Desorption Electrospray Ionization Mass Spectrometry Imaging)
Laser capture microdissection (LCM) coupled with LC-MS/MS enables proteomic analysis of defined tissue regions. Imaging mass spectrometry methods, such as MALDI-IMS, can directly visualize protein distributions on tissue sections.
(1) Advantages: simultaneous detection of hundreds of molecules while maintaining native spatial architecture.
(2) Disadvantages: limited spatial resolution (typically 10–50 µm) and reduced sensitivity for low-abundance proteins.
2. Antibody-Based Spatial Protein Detection
Techniques such as immunofluorescence (IF), multiplex immunohistochemistry (mIHC), and CODEX use multiplexed antibody labeling combined with imaging cytometry, fluorescence, or multiphoton imaging to achieve high-throughput visualization of protein spatial patterns at the tissue and cellular levels:
(1) Advantages: high spatial resolution down to the subcellular scale, especially suitable for immunology and oncology studies.
(2) Disadvantages: dependent on antibody performance and limited in the number of detectable targets.
3. Integration of Single-Cell and Spatial Information
Spatial multi-omics technologies simultaneously map transcriptomic and proteomic information in spatial context, supporting advances in precision medicine.
Application Prospects of Spatial Proteomics
1. Tumor Microenvironment Analysis
Mapping the spatial distribution of immune cells in tumors is essential for assessing responses to immunotherapies.
2. Neuroscience Research
Characterizing spatial expression patterns of proteins such as neurotransmitter-synthesizing enzymes and receptors helps elucidate the mechanisms underlying neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.
3. Drug Mechanism Investigations
Spatial proteomics enables evaluation of drug-target localization within tissues and the resulting local changes in protein expression, strengthening the development of precision therapeutics.
MtoZ Biolabs's Spatial Proteomics
MtoZ Biolabs actively tracks advances in spatial proteomic technologies. By integrating laser capture microdissection, high-sensitivity mass spectrometry platforms (such as the Orbitrap Exploris 480), and optimized sample-processing workflows, the company provides comprehensive one-stop services ranging from tissue sampling to spatial proteome profiling. These capabilities are particularly applicable to:
By incorporating spatial context, proteomics evolves from simply measuring protein abundance to determining where proteins reside. MtoZ Biolabs will continue to advance with technological innovations and support researchers in discovering more accurate biological insights within the spatial dimension.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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