Hybrid Live Cell-Supported Membrane Interfaces for Signaling Studies

A wide range of cell-microenvironmental interactions are mediated by membrane-localized receptors that bind ligands present on another cell or the extracellular matrix. This situation introduces a number of physical effects including spatial organization of receptor-ligand complexes and development of mechanical forces in cells. Unlike traditional experimental approaches, hybrid live cell-supported lipid bilayer (SLB) systems, wherein a live cell interacts with a synthetic substrate supported membrane, allow interrogation of these aspects of receptor signaling. The SLB system directly offers facile control over the identity, density, and mobility of ligands used for engaging cellular receptors. Further, application of various nano- and micropatterning techniques allows for spatial patterning of ligands. In this review, we describe the hybrid live cell-SLB system and its application in uncovering a range of spatial and mechanical aspects of receptor signaling. We highlight the T cell immunological synapse, junctions formed between EphA2- and ephrinA1-expressing cells, and adhesions formed by cadherin and integrin receptors.