Lipoparticle technology is based on the presentation of specific membrane proteins on retroviral virus-like particles (VLPs). Retroviral Gag proteins associate to form protein cores, which bud through the host cell membrane to form non-infectious VLPs (~150 nm in diameter) that display highly-expressed copies of specified membrane proteins on their surface.
- Incorporate complex membrane proteins such as GPCRs, ion channels, transporters, and viral envelope proteins
- Correctly folded membrane proteins in their native cellular membrane
- 10-100 fold concentrated membrane proteins (~50-200 pmol/mg)
- Optionally modifiable by fluorescent tags and biotinylation
Lipoparticles provide an alternative to living cells, membrane preparations, and detergent-solubilized proteins by offering concentrated membrane proteins in their native conformation. Lipoparticles are used throughout drug and antibody discovery and characterization, and have been integrated into a wide variety of existing platforms.
- Immunization for antibody elicitation
- Phage and yeast display
- Antibody screening by ELISA
- Kinetic analysis of antibody binding by biosensor
- Radioligand and fluorescent binding assays
Integral Molecular is the exclusive world-wide patent holder or licensee of all Lipoparticle patents (U.S. Patents #8,574,590, #7,763,258, #8,158,130, #8,377,691 and #8,680,244), providing broad freedom to operate. Additional patents are pending.
Please also see our Publications
Lipoparticles are virus-like particles (VLPs) containing high concentrations of specific membrane proteins in their native conformation. Lipoparticles capture conformationally-intact membrane proteins directly from the cell surface, enabling these complex proteins to be manipulated as soluble proteins. Lipoparticles are produced with specified membrane proteins on a custom basis, or are available from a selected catalog of ReadyReceptors. Sample kits are also available for purchase for preliminary application testing.
Applications include antibody phage/yeast panning, immunization, biosensor studies, and high-throughput screening.
- Custom Lipoparticles
- ReadyReceptor Lipoparticles
- Sample Kits
Using our optimized production process, Lipoparticles are engineered to incorporate high concentrations of specified membrane proteins. This process includes optimization of membrane protein expression and incorporation.
Each batch of Lipoparticles is assessed using up to 16 quality control metrics, ensuring homogeneity, purity and target protein integrity. With over 5,000 membrane proteins encoded in the human genome, we have the capacity to routinely incorporate a wide variety of specified membrane proteins.
To request a quote, contact us.
Pre-validated Lipoparticles listed below contain optimized, highly-expressed membrane proteins and are available for rapid delivery. ReadyReceptor Lipoparticles are produced and validated using all of the stringent quality metrics used for Custom Lipoparticle production.
|Class||Receptor||Description||Catalog No. (10,000 U)|
|CaS receptor C||Calcium Sensing||RR-0562|
|GLP-1R C||Glucagon-like peptide-1 Receptor||RR-1090|
|GCGR C||Glucagon Receptor||RR-0999|
|GAL1 receptor C||Neuropeptide Receptor||RR-1067|
|FZD4 C||Wnt Pathway||RR-1302|
|Ion Channel||Hv1 C||Voltage Gated H +||RR-0678|
|TRPC4 N||Nonspecific Cation Channel||RR-1054|
|TRPM4||Nonspecific Cation Channel||RR-1333|
|K2P1.1 C||Potassium Channel||RR-1225|
|K2P4.1 C||Potassium Channel||RR-1331|
|P2X2 C||ATP Purinoceptor||RR-1181|
|RTK||ALK2 C||Activin Receptor||RR-0850|
|1-TM||ACVR1||Activin A Receptor, Type I||RR-0850|
|CD19 C||B-Cell Activation||RR-0553|
|CD27 C||B-Cell Activation||RR-0655|
|LRP6 C||Wnt Pathway||RR-0853|
|ST2L||IL-1 Receptor Family||RR-0653|
|4-TM||CD81||Hepatitis C Attachment||RR-0341|
|CD20 C||B-Cell Activation||RR-1179|
|Claudin-4 C||Tight Junction||RR-0686|
|Claudin-6 C||Tight Junction||RR-0949|
|Viral Protein||RSV-F C||Respiratory Syncytial Virus||RR-0891|
|Influenza M2 A/Udorn/307/1972||Ion Channel||RR-0929|
|Influenza M2 A/HK/156/1997 C||Ion Channel||RR-0179|
|Chikungunya Virus C||Viral Envelope||RR-0945|
|HCV E1 C||Viral Envelope||RR-1184|
|HCV E2 C||Viral Envelope||RR-1064|
|Ross River Virus||Viral Envelope||RR-1136|
|Transporter||ABCA1||ATP-Binding Cassette Transporter||RR-0965|
|Custom Lipoparticle Services Available|
Lipoparticle sample kits containing prototype GPCRs and matched Null Lipoparticles are available for overnight delivery to enable application optimization and small-scale testing.
|Sample Kit||Class||Cat. No||Size|
|CXCR4 C||GPCR||LEV-101||400 U|
|CCR5 C||GPCR||LEV-102||400 U|
To request a quote, contact us.
Q: What are Lipoparticles?
A: Lipoparticles are non-infectious virus-like particles (VLPs) containing high concentrations of specific membrane proteins in their native conformation.
Q: How many membrane proteins are incorporated onto Lipoparticles?
A: Lipoparticles typically contain 50-200 pmol/mg of a specific target membrane protein, which corresponds to approximately 50-200 specific receptors per Lipoparticle. Membrane protein incorporation rate is directly related to the amount of the membrane protein expressed at the cell surface.
Q: Are target membrane proteins on Lipoparticles conformationally-intact?
A: Yes, target membrane proteins are conformationally-intact because they are incorporated onto the surface of Lipoparticles directly from the cell surface and are never extracted or refolded. Lipoparticles are usually produced from human cell lines so receptors also contain native post-translational modifications. Conformational integrity is demonstrated using conformation-dependent antibodies or ligand binding, depending on the receptor and available reagents.
Q: Do Lipoparticles contain non-specific membrane proteins?
A: Lipoparticles bud from the cell surface, so contain specific membrane proteins of interest as well as additional membrane proteins from the cells used for production. The effects of non-specific membrane proteins are minimized by over-expression of the membrane protein of interest, the use of alternative cell types where necessary, and the use of Null Lipoparticles that do not contain the membrane protein of interest as negative controls.
Q: What is inside the Lipoparticle?
A: The Lipoparticle interior is composed of a well-defined polyprotein (retroviral Gag) that drives the production of Lipoparticles within cells. Gag is necessary and sufficient for Lipoparticle production. Cellular cytoplasmic proteins are generally not incorporated into Lipoparticles.
Q: What membrane proteins can and cannot be incorporated into Lipoparticles?
A: All plasma membrane proteins tested to date can be incorporated into Lipoparticles, although cellular expression levels influence incorporation levels. Membrane proteins that are not expressed on the cell surface are not incorporated. Incorporation of the target membrane protein is characterized during initial production optimization experiments to ensure that sufficient levels are achieved for the application.
Q: Can complexes of multiple membrane proteins (e.g. 2 or more) be incorporated?
A: Yes, two or more membrane proteins can be incorporated simultaneously while maintaining their association as multi-protein complexes.
Q: Are Lipoparticle lipid membranes different from cellular lipid membranes?
A: Lipoparticle membranes are similar to lipid raft regions of cellular membranes and are enriched in cholesterol and sphingolipids.
Q: How stable are Lipoparticles?
A: Lipoparticle stability is comparable to other purified proteins. Lipoparticles are stable for at least 6 months when refrigerated or frozen. Like most lipid structures, Lipoparticles will be disrupted by detergents, but are stable in the presence of small amounts (<5%) of common additives (e.g. DMSO, ethanol). Lipoparticle suspensions will appear as an opaque solution and should be gently mixed prior to use. Excessive vortexing, dilution, and filtration of Lipoparticles should be avoided to minimize sample loss.
Q: Are Lipoparticles safe?
A: Lipoparticle are safe when handled and used appropriately. Lipoparticles are not viruses. Although they are made using a viral protein, Lipoparticles lack numerous components that would be required for infection, replication, or integration, including a genome, an envelope protein, LTR regions, and many enzymatic proteins. Lipoparticles should be treated similar to other purified proteins of biological origin. In addition, Lipoparticles use proteins derived from a retrovirus that is not known to infect or cause disease in humans. Nevertheless, Lipoparticles are derived from biological sources and should be handled with caution within a biological laboratory environment. Lipoparticles should not be used in humans.
Q: Can I modify or label Lipoparticles?
A: Lipoparticles are non-living biochemical reagents, so can readily be modified, either during production or after purification. Lipoparticles are available from Integral Molecular biotinylated or fluorescently labeled.
Q: How can I try Lipoparticles?
A: We would be happy to discuss how Lipoparticles can advance your discovery work. Contact us to purchase Lipoparticle evaluation samples. Once you have completed your evaluation, we can custom produce Lipoparticles with your membrane protein(s) of interest.
Q: Can I buy engineered membrane proteins from Integral Molecular?
A: Integral Molecular specializes in engineering difficult and toxic membrane proteins for improved surface trafficking and Lipoparticle incorporation. We routinely engineer membrane proteins for internal projects, partner projects, and customer-based research projects. Please feel free to discuss with us how we can engineer customized membrane proteins to best suit your needs.