A Microbead Supported Membrane-Based Fluorescence Imaging Assay Reveals Intermembrane Receptor-Ligand Complex Dimension with Nanometer Precision

Langmuir. 2016 Jul 5;32(26):6775-80. doi: 10.1021/acs.langmuir.6b01377. Epub 2016 Jun 20.

Abstract

Receptor-ligand complexes spanning a cell-cell interface inevitably establish a preferred intermembrane spacing based on the molecular dimensions and orientation of the complexes. This couples molecular binding events to membrane mechanics and large-scale spatial organization of receptors on the cell surface. Here, we describe a straightforward, epi-fluorescence-based method to precisely determine intermembrane receptor-ligand dimension at adhesions established by receptor-ligand binding between apposed membranes in vitro. Adhesions were reconstituted between planar and silica microbead supported membranes via specific interaction between cognate receptor/ligand pairs (EphA2/EphrinA1 and E-cadherin/anti-E-cadherin antibody). Epi-fluorescence imaging of the ligand enrichment zone in the supported membrane beneath the adhering microbead, combined with a simple geometrical interpretation, proves sufficient to estimate intermembrane receptor-ligand dimension with better than 1 nm precision. An advantage of this assay is that no specialized equipment or imaging methods are required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry*
  • Antigens, CD
  • Cadherins / chemistry*
  • Ephrin-A1 / chemistry*
  • Ephrin-A2 / chemistry*
  • Humans
  • Microspheres*
  • Optical Imaging*
  • Receptor, EphA2
  • Silicon Dioxide / chemistry*

Substances

  • Antibodies
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • EPHA2 protein, human
  • Ephrin-A1
  • Ephrin-A2
  • Silicon Dioxide
  • Receptor, EphA2