Crosslinking-Assisted IP-MS
Choose this workflow when You have a known bait protein and need to identify associated proteins that may be weak, transient, or lost during lysis.
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Protein Interaction Analysis Service
Crosslinking Mass Spectrometry Protein Interaction Analysis Service
Crosslinking-assisted LC-MS/MS workflows for discovering protein interactors, comparing condition-dependent complexes, and adding structural contact evidence within cells, tissues, or other biologically relevant sample contexts.
Use this service when a protein complex may be weak, transient, membrane-associated, or sensitive to lysis. Crosslinking can help stabilize associations before enrichment or analysis, which can help preserve associations that may otherwise be disrupted during extraction or sample processing.
- Discover candidate interactors around a known bait protein or protein complex.
- Compare interaction profiles across treatment, stimulation, time-course, or disease-control groups.
- Support Co-IP, pull-down, or tagged enrichment projects where native complexes are difficult to preserve.
DiscoveryNative-cell ContextWeak / Transient PPILow-abundance TargetsPilot Available
Research experience
Supporting interaction proteomics projects for academic and industry research groups
Researchers from leading academic and industry organizations have worked with MtoZ Biolabs on protein interaction and crosslinking mass spectrometry projects. Project scope, workflow, and controls are tailored to each study.
When This Service Is a Good Fit
Designed for interaction proteomics projects where crosslinking can help preserve weak, transient, membrane-associated, or condition-dependent protein associations.
Known bait, unknown partners
You have a target protein and need a ranked list of candidate interactors from cells, tissue, or another biological model.
Weak or transient complexes
You expect short-lived, stimulus-dependent, or lysis-sensitive associations that may not survive standard Co-IP conditions.
Treatment-dependent changes
You want to compare how a drug, mutation, stimulation, stress condition, or time point changes the interaction profile.
Membrane or low-abundance targets
You work with proteins that are difficult to enrich cleanly and need a project review before committing to a full-scale workflow.
Complex-level discovery
You need candidate subunits, accessory proteins, or complex-associated proteins for downstream validation.
Contact-site evidence
You need crosslinked peptide evidence to support spatial proximity, domain-level interpretation, or structural modeling.
Choose the Right Crosslinking Workflow
Select a route based on your bait, sample state, enrichment strategy, and whether the goal is discovery, comparison, stabilization, or contact-site evidence.
Not sure which route fits? Choose "Not sure — recommend a workflow" in the quote form and share your sample type, bait protein, and expected result.
In-Cell / In-Tissue Crosslinking Discovery
Choose this workflow when You want to capture interactions in their biological context before extraction, especially across treatment, stimulation, tissue-state, or time-course groups.
Click to preview →In-Lysate Crosslinking
Choose this workflow when Your sample is already lysed or in vivo crosslinking is not practical, but stabilization during handling may improve complex recovery.
Click to preview →XL-MS Contact Mapping
Choose this workflow when You need peptide-level proximity evidence for contact-site mapping, domain-level interpretation, or structural modeling.
Click to preview →
Workflow preview
Select a route above
After you select a route, this panel will summarize the best next step and carry that choice into the quote form.
Service Workflow
A project path from feasibility review and sample planning to crosslinking, enrichment, LC-MS/MS acquisition, data analysis, and reporting.
Feasibility Review
Confirm the project goal, bait, sample type, and workflow fit.
Sample Planning
Define sample input, controls, replicates, and handling strategy.
Crosslinking
Apply the selected in vivo, in-tissue, or in-lysate crosslinking route.
Enrichment
Perform IP, pull-down, or complex enrichment based on the approved design.
LC-MS/MS Acquisition
Acquire peptide or crosslinked peptide data with the matched MS workflow.
Data Analysis & Report
Review QC and interaction evidence, then deliver result tables, figures, and report.
A simplified project path from sample review to crosslinking, enrichment, LC-MS/MS acquisition, and interpretation-ready reporting.
What to Send Us — By Workflow
Recommended submission formats, planning ranges, and shipping considerations for common in vivo crosslinking interaction proteomics workflows.
| Workflow | Sample Type | Sample Amount |
|---|---|---|
| Crosslinking-Assisted IP-MS | Cells, tissue, organoids, or other biological samples with antibody-, tag-, or pull-down-based enrichment. | 1- 5 × 10⁷ cells ,100-150 µl cell pellet or 50 - 200 mg tissue per IP condition as a typical planning range. |
| In-Cell / In-Tissue Crosslinking Discovery | Cultured cells, treated cells, tissue pieces, organoids, or matched biological groups for condition-based discovery. | Common planning range: 1-10 × 10⁷ cells per condition or 100-150 ul cell pellet per condition; tissue input is typically reviewed by available mass and target abundance. |
| In-Lysate Crosslinking | Clarified lysate, extracted fraction, or prepared sample with defined buffer conditions. | 0.5 - 2 mg total protein per condition before enrichment as a common planning range. |
| XL-MS Contact Mapping | Purified complex, enriched complex, or crosslinked complex sample suitable for contact-site analysis. | 100 µg target complex when available; higher starting input may be needed for lower-abundance material. |
Limited sample?
Send the amount you have. Final input is reviewed based on target abundance, enrichment efficiency, background level, and required detection depth.
Results & Deliverables
Deliverables are tailored to the selected workflow and study design.
Candidate interactor table
Protein IDs, names, scores or intensity, enrichment patterns.
Group comparison results
Relative differences across treatment, control, time-course, mutant, or disease-control groups where the study design supports comparison.
Crosslinked peptide evidence
For XL-MS projects, detected crosslinked peptide pairs, site-level links where identified, spectral evidence, and mapping-ready tables.
QC summary
Sample processing notes, LC-MS/MS acquisition summary, identification metrics, replicate assessment.
Figures and report
Tables and visual summaries for candidate prioritization, comparison interpretation, and follow-up experiment planning.
Raw and processed files
Data files and processed result tables can be provided according to project scope and reporting needs.
Platform & Capabilities
Integrated project design, LC-MS/MS instrumentation, and QC review for crosslinking-based interaction proteomics.
Project Support
Start Project Review
From workflow selection to result interpretation
Each project is reviewed around the target, sample state, enrichment strategy, controls, and expected evidence level.
Workflow recommendation
Crosslinking-assisted IP-MS, in-cell/in-tissue discovery, in-lysate stabilization, or XL-MS mapping.
Enrichment review
Antibody, tag, beads, pull-down format, input, and negative control planning.
QC checkpoints
Sample handling, enrichment background, LC-MS/MS performance, and replicate behavior.
Result guidance
Candidate prioritization, confidence factors, and follow-up validation suggestions.
Representative Platform
LC-MS/MS Platforms & Analytical Capabilities
UltiMate3000 RSLCnano Orbitrap Fusion™ Lumos™ Tribrid™
Precision nanoLC-MS/MS for sensitive, in-depth peptide characterization
Vanquish Neo Orbitrap Fusion™ Lumos™ Tribrid™
Robust low-flow LC-MS/MS for reproducible analysis of complex peptide samples
Vanquish Neo Orbitrap Exploris 480
High-resolution LC-MS/MS for confident peptide identification and quantification
Vanquish Neo Astral
High-speed, high-sensitivity LC-MS/MS for deep proteome coverage
Control-aware filteringReplicate reviewCoverage assessmentReport-ready tables
Result Considerations
A brief guide to what crosslinking-MS results can support, what they cannot confirm alone, and which factors affect confidence.
What results can support
Candidate protein associations, proximity evidence, and condition-related interaction changes.
What needs validation
Direct binding, functional relevance, and mechanism usually require follow-up experiments.
What affects confidence
Target abundance, sample quality, input amount, enrichment performance, controls, and MS coverage.
Standard Co-IP-MS vs Crosslinking-Assisted IP-MS
A quick guide to when crosslinking may help. In both cases results provide candidate association evidence; direct binding usually requires orthogonal validation.
| Scenario | Standard Co-IP-MS | Crosslinking-Assisted IP-MS |
|---|---|---|
| Stable complexes | Often suitable | Also suitable |
| Weak / transient interactions | May be lost during extraction | May be better preserved |
| Lysis-sensitive complexes | Higher risk of disruption | Stabilization may help |
| Interpretation | Association evidence | Association evidence with crosslinking context |
| Optimization burden | Lower | Higher (crosslinker, conditions, controls) |
FAQs
Frequently asked questions about In Vivo Crosslinking Protein Interaction Analysis
Standard Co-IP-MS enriches a bait protein and associated proteins after extraction. Crosslinking-assisted workflows add a stabilization step before or during sample processing, which can help preserve weak, transient, or lysis-sensitive associations.
Interactor discovery results provide candidate association evidence. Direct binding usually requires orthogonal validation such as reciprocal IP, purified-protein binding assays, mutagenesis, targeted MS, or functional experiments. XL-MS contact evidence can strengthen proximity interpretation when crosslinked peptides are confidently detected.
The control plan depends on the workflow. Common options include input, IgG, beads-only, tag-only, untreated, non-crosslinked, and matched biological controls. Comparison studies should use consistent sample handling across groups.
For bait-centered IP-MS, a reliable antibody, tag, or pull-down route is important. If no enrichment route is available, share the target and sample information so we can discuss whether another strategy is more suitable.
A pilot is recommended for low-abundance targets, untested antibodies or tags, rare samples, membrane proteins, complex tissues, or projects where the crosslinking and enrichment route still needs optimization.
Yes. Treatment-control, mutant-wild type, dose-response, stimulation, and time-course comparisons can be designed when sufficient replicates and matched controls are available.