Combined confocal fluorescence spectroscopy, photon counting histogram (PCH) analysis, and epifluorescence microscopy is used to quantitatively study the effect of the native ligands vitronectin and fibronectin on domain�specific sequestration and oligomerization state of integrins (av�3 and a5�1) in polymer-tethered lipid bilayer systems containing raft-mimicking lipid mixtures.  Specifically, experiments were conducted on integrins in bilayer-spanning raft-mimicking domains (TYPE I), binary cholesterol-lipid mixtures (TYPE II), and monolayer raft-like domains (TYPE III). Our experiments show that av�3 and a5�1 sequester preferentially to liquid disordered domains in the absence of ligands.  Remarkably, ligand addition causes substantial changes in integrin sequestering without altering their largely monomeric state in the model membrane. Comparing experiments on TYPEs I-III also demonstrate that alterations in lipid heterogeneity may have substantial impact on ligand-mediated integrin sequestering, thus highlighting the importance of lipid composition on the functionality of individual membrane receptors.

Ligand-mediated sequestering of integrins in raft-mimicking lipid mixtures

243rd National Meeting (2012)

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