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lipoparticle process


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

Lipoparticle Applications

  • Phage panning
  • Serum response to Lipoparticles
  • Kinetic analysis of binding
  • Conformational antibody binding
  • Radioligand binding
  • Quality controlled production

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

Lipoparticle Product

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

Custom Lipoparticles

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.

ReadyReceptor Lipoparticles

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)
GPCR α2A-AR C Adrenoceptor RR-0910
ß2-AR N,C Adrenoceptor RR-0574
CaS receptor C Calcium Sensing RR-0562
CCR1 C Chemokine RR-0968
CCR2b Chemokine RR-0125
hCCR5 C Chemokine RR-0190
mCCR5 C Chemokine RR-0835
rhCCR5 C Chemokine RR-0895
CCR6 C Chemokine RR-0822
CCR10 N,C Chemokine RR-0193
CXCR2 Chemokine RR-0943
CXCR3 Chemokine RR-0132
CXCR4 C Chemokine RR-0830
CXCR7 C Chemokine RR-0656
mCXCR4 Chemokine RR-2194
GLP-1R C Glucagon-like peptide-1 Receptor RR-1090
GCGR C Glucagon Receptor RR-0999
GAL1 receptor C Neuropeptide Receptor RR-1067
5-HT2C Serotonin Receptor RR-1498
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
DC-SIGN C Lectin RR-0057
DC-SIGNR Lectin RR-0056
LRP6 C Wnt Pathway RR-0853
hTL1A TNF Ligand RR-0819
mTL1A TNF Ligand RR-0817
DR5 TNF-family Receptor RR-0818
ST2L IL-1 Receptor Family RR-0653
4-TM CD81 Hepatitis C Attachment RR-0341
CD20 C B-Cell Activation RR-1179
Claudin-1 Tight Junction RR-0825
Claudin-3 Tight Junction RR-0733
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
GLUT1 Glucose Transporter RR-0777
GLUT4 Glucose Transporter RR-0961
Custom Lipoparticle Services Available

Epitope tags: N=amino terminal, C=carboxy terminal
Lipoparticles can be modified with (B) Biotin or (F) Fluorescence

Sample Kits

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.

Lipoparticle FAQs

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.