Membrane proteins are the field's biggest drug-discovery prize. They are heavily involved in transport, signaling, and cell-cell recognition, and by some estimates, they represent over 60% of known drug targets and roughly 90% of antibody-based drug targets.
However, as any researcher knows, they are also uniquely hard to work with. Multi-pass transmembrane proteins, in particular, aggregate readily once pulled out of a membrane, and their 3D conformation depends heavily on their surrounding lipid environment. Traditional extraction methods relying on detergents strip away these essential annular lipids and push proteins into non-native conformations.
Native Conformation, Zero Detergent
Our Styrene-Maleic Anhydride (SMA) nanodisc platform delivers multi-pass transmembrane proteins exactly as they exist in the HEK293 cell membrane following recombinant expression.
Instead of forcing your target through a fragile "detergent window," our synthetic polymer is added straight to the cell membrane, where it cuts out and wraps a patch of native membrane, protein and all. Isolated directly from HEK293 cells via this gentle, detergent-free process, the multi-pass membrane proteins are subsequently encapsulated by SMA to ensure their stability. The protein never leaves the cellular membrane, keeping its real native lipids and true native conformation intact.
How It Works: Expression & Structure
Native Expression: Multi-pass transmembrane proteins are recombinantly expressed exactly as they exist in the HEK293 cell membrane.
Detergent-Free Extraction: Targets are isolated directly from cells via a gentle process that preserves their endogenous lipid environment and correct conformational states.
SMA Encapsulation: The proteins are encapsulated by Styrene-Maleic Anhydride (SMA) into uniform, soluble nanoparticles that eliminate extraction interferences.
Assay-Ready: These stable nanodiscs provide lot-to-lot reliability for antibody screening and functional characterization via SPR, BLI, and ELISA.
Key Advantages of KACTUS SMA Nanodisc Platform
Native Structure & Conformation: By retaining native annular lipids, our platform ensures the functional relevance of your target proteins.
Unmatched Stability: While traditional detergent micelles degrade over minutes to hours, nanodiscs retain protein activity for days to weeks. These uniform soluble nanoparticles eliminate extraction interferences while maintaining biological activity.
Lot-to-Lot Reliability: Ensuring consistent performance from lot to lot, our nanodiscs provide the reliability essential for therapeutic antibody drug discovery and development.
Ready for Assays: His-tag and biotinylation tags are available to seamlessly integrate into your workflow.
Built For High-Performance Applications
Our nanodiscs provide the biological relevance you need for critical downstream applications:
Antibody Screening: Screen with confidence knowing your target reflects its true biological state.
Functional Characterization: Achieve precise analysis at the molecular level.
Standard Assay Compatibility: Fully optimized for SPR, BLI, ELISA, and other standard platforms. Because the target reaches the sensor surface never having left its native lipid environment, SPR and BLI binding kinetics reflect true affinity rather than a reconstitution artifact.
Improved Accuracy in your Antibody Screening
TCR-CD3 Nanodiscs: Eliminate Off-Target Antibodies
Once a high-titer immune response is achieved via VLP immunization, the challenge shifts to high-resolution screening. KACTUS Nanodiscs provide the refined, detergent-free environment necessary for the downstream selection of top-tier leads.
By capturing the full TCR-CD3 complex within a discrete lipid bilayer, our nanodiscs offer a stable, soluble format optimized for:
- High-Throughput Assays: Perfectly suited for ELISA, SPR, and BLI, offering low background noise and improved purity relative to VLPs.
- Native Lead Validation: Ensures the antibodies selected during downselection maintain high affinity for the TCR/CD3 complex exactly as it appears on a live T cell.
Product Validation Data
High Protein Binding Affinity
We rigorously verify the bioactivity of our complex multi-pass targets, such as the Human NaPi2b/SLC34A2 Nanodisc, via ELISA and SPR. SPR analysis demonstrates native-state, high-affinity binding (KD = 2.64 nM) without the need for artificial lipid reconstitution.
Outstanding Temperature Stability
Our native lipid encapsulation protects sensitive multi-pass targets from rapid degradation. As demonstrated by our Human CCR4 Nanodisc, functional binding activity remains completely stable even after 7 days of continuous incubation at 37°C.
Robust Freeze-Thaw Tolerance
Complex membrane proteins are notoriously fragile, but our synthetic polymer ensures reliable stability during routine storage and laboratory handling. Our Human GPRC5D Nanodisc maintains consistent, high-affinity binding profiles even after undergoing 5 complete freeze-thaw cycles.
Strict Batch-to Batch Consistency
We ensure consistent performance from lot to lot, which is critical for providing the reliability essential for therapeutic antibody drug discovery. Multiple production runs of our highly complex KRAS G12D TCR & CD3 Complex Nanodisc demonstrate virtually identical binding activity across different manufacturing batches.
How We Compare: SMA Copolymer vs. Traditional Methods
| Feature | Our SMA Copolymer Nanodiscs | Traditional MSP Nanodiscs | Detergent Micelles |
|---|---|---|---|
| Extraction Method | Polymer wraps native membrane directly. | Protein extracted with detergent, then rebuilt. | Extracted with harsh detergents. |
| Lipid Environment | Preserves endogenous cellular lipids. | Uses artificial, reconstituted lipids. |
Strips away annular lipids. |
| Detergent Required? | No detergent needed at all. | Requires detergent step initially. | Yes, heavy detergent use. |
| Conformational Fidelity | Highly native; avoids structural deviations. | Forced insertion can create deviations from true native conformation. | Often pushes proteins into non-native conformations. |
Available Products
Custom Membrane Protein
Nanodisc FAQs
1. What is an SMA copolymer nanodisc?
An SMA nanodisc is a uniform soluble nanoparticle where a multi-pass transmembrane protein is encapsulated by a Styrene-Maleic Anhydride (SMA) synthetic polymer. This synthetic polymer is added directly to the cell membrane, where it cuts out and wraps a patch of native membrane, protein and all. This gentle process avoids extraction interferences and keeps the target protein in its endogenous lipid environment.
2. Why should I choose SMA nanodiscs over traditional MSP nanodiscs or detergents?
Detergents can strip away annular lipids and often push proteins into non-native conformations. Traditional MSP (membrane scaffold protein) nanodiscs also require the target protein to first be purified in detergent, subjecting it to a fragile detergent window before it is rebuilt into artificial lipids. Our SMA platform bypasses detergents entirely, keeping the protein's native lipids and true native conformation intact. This detergent-free approach retains protein activity for days to weeks, whereas detergent micelles degrade over minutes to hours.
3. What expression system is used for your nanodisc proteins?
We express our recombinant multi-pass membrane proteins in HEK293 cells. We utilize mammalian cells because they more faithfully replicate native protein folding and provide crucial post-translational modifications (such as glycosylation) that are necessary for complex multi-pass targets.
4. Are tags available for immobilization or detection?
Yes, His-tags and biotinylation tags are available on our nanodisc proteins to seamlessly integrate into your specific capture workflows.
5. What downstream applications are these nanodiscs optimized for?
Our nanodiscs provide consistent lot-to-lot performance and biological relevance essential for therapeutic antibody drug discovery and development. They are utilized for antibody screening and functional characterization at the molecular level. The platform is validated for standard assays including SPR, BLI, and ELISA. Because the protein reaches the sensor surface in its native lipid environment, binding kinetics reflect true affinity rather than an artifact of reconstitution.
6. Do you offer custom nanodisc production for novel or "undruggable" membrane proteins?
Yes. We offer custom production for full-length, multi-pass membrane proteins. We express your custom target in mammalian cells to ensure proper folding and correct post-translational modifications. We then utilize our detergent-free SMA platform to extract and encapsulate the protein, delivering your target securely locked in its native conformation.
7. What types of membrane proteins are best suited for this platform?
Our platform is highly tailored for complex multi-pass transmembrane proteins (proteins with two or more transmembrane helices). While researchers can often get away with using just the extracellular domain (ECD) for single-pass proteins, multi-pass targets generally need to be studied full-length. Because these complex proteins aggregate readily outside of a membrane and depend heavily on their surrounding lipid environment for their 3D conformation, our native nanodisc environment is essential for their stability and functional characterization.
8. Are these nanodiscs suitable for screening AI-generated protein binders?
Absolutely. AI-generated binders are typically designed against a modeled or predicted epitope. If you screen these against a target that has been distorted by detergents or artificial lipid reconstitution, you risk generating false negatives (real binders that fail) or false positives (binders that only recognize an artifact of reconstitution). Because our SMA copolymer nanodiscs preserve the true native state and endogenous annular lipids, they provide the strict conformational fidelity required for accurate binding-affinity work.
9. Do copolymer nanodiscs have any limitations compared to MSP nanodiscs?
Because SMA copolymers extract whatever patch of native membrane they happen to wrap, they are less uniform in size and defined composition than MSP discs. While this modest particle heterogeneity is highly tolerated by applications like ELISA or SPR, copolymer discs are not ideal for applications requiring tight particle-to-particle consistency, such as high-purity Cryo-EM alignments.
