Lawrence Berkeley National Laboratory masthead A-Z Index Berkeley Lab masthead U.S. Department of Energy logo Phone Book Jobs Search
Tech Transfer
Licensing Interest Form Receive Customized Tech Alerts

Membrane-Derivatized Colloids for the Detection and Analysis of Cell Membrane Binding Interactions

IB-1919

APPLICATIONS OF TECHNOLOGY:

   
 
  Schematic showing a single individual silica bead coated with a phospholipid bilayer membrane
  • Drug discovery and lead optimization
  • Antibody QA/QC
  • Biosensors for on-site pathogen detection and biodefense applications
  • Medical diagnostics


ADVANTAGES:

  • Adaptable for use in high-throughput protocols
  • Sensitivity down to picomolar concentrations: allows screening of receptors at native concentrations that is not possible with SPR
  • Easy to quantify the relative strengths of receptor-ligand interactions
  • Detection is label-free and power-free

ABSTRACT:

Jay Groves and co-workers at Berkeley Lab and UC Berkeley have invented a novel means for analyzing the molecular interactions on lipid membrane surfaces. The technology enables rapid, high throughput screening of compounds that bind a given membrane receptor protein, making it of great potential utility in drug discovery and development.

The biological processes occurring at the cell membrane are the subject of intense interest, with most drugs and infectious diseases targeting the cell membrane. Experimental analysis of the membrane surface has previously been performed using lipid membranes supported on solid substrates, such as silica or polymers. However, this method requires techniques such as surface plasmon resonance (SPR) or total internal reflection fluorescence microscopy (TIRF) to detect the associated interactions. SPR and TIRF have a number of associated drawbacks, including: high cost, sub-optimal sensitivity, and incompatibility with high-throughput screening processes.

The Berkeley Lab technology surmounts these problems by using colloidal particles coated with the membrane phospholipid bilayer. This colloid-lipid bilayer closely mimics the natural fluidity of the actual cell membrane. Receptor proteins can be readily embedded in the bilayer coating for further functional analysis, such as the screening of putative ligands. The specific binding of a ligand to an embedded receptor protein then triggers a change in the distribution of the lipid-coated beads.

These properties confer a number of key advantages over existing technologies. Crucially, changes can be easily visualized using a conventional light microscope or by high throughput screening devices, such as an imaging plate reader. Also of key importance is the significantly improved sensitivity over SPR by at least two orders of magnitude. This enables the screening of ligands for certain receptors such as G-protein coupled receptors at their native concentration which is not possible using SPR. Lastly, the relative affinity of a given receptor for different ligands can also be easily quantified by measuring the spatial distribution of the beads.

The system could be used as a rapid, cost-effective, and labor-saving means of screening for drugs that may bind a given receptor protein of therapeutic interest. The binding capability of protein drugs, such as monoclonal antibodies can also be measured. Furthermore, the high sensitivity of the system, down to picomolar concentrations, lends itself to biosensing applications such as in biodefense.

STATUS:

FOR MORE INFORMATION:

Baksh, M.M., Jaros, M., Groves, J.T., "Detection of Molecular Interactions at Membrane Surfaces Through Colloid Phase Transitions," Nature 2004, 427, 139-141.

Bayerl, T.M., "A Glass Bead Game," Nature 2004, 427, 105-106.

REFERENCE NUMBER: IB-1919

See More Biotech & Medicine Technologies
Last updated: 09/17/2009