Abstract
Lateral compositional and physicochemical heterogeneity is a ubiquitous feature of cellular membranes on various length scales, from molecular assemblies to micrometric domains. Segregated lipid domains of increased local order, referred to as rafts, are believed to be prominent features in eukaryotic plasma membranes; however, their exact nature (i.e. size, lifetime, composition, homogeneity) in live cells remains difficult to define. Here we present evidence that both synthetic and natural plasma membranes assume a wide range of lipid packing states with varying levels of molecular order. These states may be adapted and specifically tuned by cells during active cellular processes, as we show for stimulated insulin secretion. Most importantly, these states regulate both the partitioning of molecules between coexisting domains and the bioactivity of their constituent molecules, which we demonstrate for the ligand binding activity of the glycosphingolipid receptor GM1. These results confirm the complexity and flexibility of lipid-mediated membrane organization and reveal mechanisms by which this flexibility could be functionalized by cells.
Highlights
The membrane raft hypothesis proposes a laterally heterogeneous structure for biological membranes [1], with lipid-induced membrane domains being responsible for functional compartmentalization of cellular trafficking and signaling activities in a wide variety of cellular contexts [2,3]
It was recently observed that biological membranes can assume a number of distinct lipid packing states (13) and that these may correspond to domains in live cell membranes [14]
Having shown that biomimetic and biologically derived membranes have the potential to form a large number of domains with distinct physical properties (Figs 1 and 2), and that such domains can be generated by cellular activity (Fig 3), we addressed the functional consequences of variable lipid packing by investigating its role on the partitioning and bioactivity of membrane molecules
Summary
The membrane raft hypothesis proposes a laterally heterogeneous structure for biological membranes [1], with lipid-induced membrane domains being responsible for functional compartmentalization of cellular trafficking and signaling activities in a wide variety of cellular contexts [2,3]. The physicochemical nature of raft-mediated membrane heterogeneity and its direct impact on cell function remains difficult to define. The original and still predominant method for measuring raft composition in live cells is indirectly via their detergent resistance [4], wherein the differential solubility of membrane components to non-ionic detergents is inferred to be related to the localization of those components in raft domains. This interpretation is complicated by PLOS ONE | DOI:10.1371/journal.pone.0123930. This interpretation is complicated by PLOS ONE | DOI:10.1371/journal.pone.0123930 April 23, 2015
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