Membrane Heterogeneity and its Role in Immune Signaling Elucidated by Spectral Imaging

Abstract

Nature of the cellular membrane heterogeneity has been a long-standing question in cell biology. One crucial measure for the membrane heterogeneity is the lipid packing. Measuring changes of lipid packing in the plasma membrane during cellular events has been an important part of elucidating the biological function of membrane physical chemistry. Here, we apply conventional and spectral imaging to figure out the nature of membrane heterogeneity and its role in immune signalling events.We observe bio-membranes sampling different lipid packing states that form coexisting domains (i.e., relatively ordered and disordered domains) with a variety of distinct compositions and functional characteristics. We first investigate the connection between membrane composition and lipid packing in synthetic liposomes and show that both the relatively ordered and disordered phase, and the difference between them, are tuned by lipid composition. We then give an example of live cells regulating the lipid packing phenotypes of their plasma membranes, accessing a variety of both ordered and disordered domains as a function of cellular activity. Finally, we find that in both synthetic and natural membranes, the tunable interdomain lipid packing disparity (i.e. the difference between coexisting domains) regulates component partitioning between domains and the functionality of membrane embedded lipidic receptors. By applying advanced image processing with spectral imaging, we show that even the marginal modulation of membrane heterogeneity is crucial for immune signalling events such as FCR and B-cell signalling.Membrane heterogeneity is an organizing principle for the membrane bio-activity by either concentrating certain molecules in transient domains or by physically adjusting the conformity of the molecules to favour or hinder their interactions in the membrane.