Abstract
Liquid-ordered (LO) domains reconstituted in model membranes1,2,3,4,5,6 have provided a useful platform for in vitro studies of the lipid-raft model7,8,9, in which signalling membrane molecules are thought to be compartmentalized in sphingolipid- and cholesterol-rich domains. These in vitro studies, however, have relied on an uncontrolled phase-separation process that gives a random distribution of LO domains. Obviously, a precise control of the size and spatial distribution of the LO domains would enable a more systematic large-scale in vitro study of the lipid-raft model. The prerequisite for such capability would be the generation of a well-defined energy landscape for reconstituting the LO domain without disrupting the two-dimensional (2D) fluidity of the model membrane. Here we report controlling the reconstitution of the LO domains in a spatially selective manner by predefining a landscape of energy barriers using topographic surface modifications. We show that the selective reconstitution spontaneously arises from the 2D brownian motion of nanoscale LO domains and signalling molecules captured in these nanodomains, which in turn produce a prescribed, concentrated downstream biochemical process. Our approach opens up the possibility of engineering model biological membranes by taking advantage of the intrinsic 2D fluidity. Moreover, our results indicate that the topographic configuration of cellular membranes could be an important machinery for controlling the lipid raft in vivo.
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Acknowledgements
T.-Y.Y. thanks T. Ha and C.-J. Yu for valuable help and discussions, and M. K. Nahas, M. C. McKinney and B. Okumus for critical reading. This work was supported in part by the Korea Science and Engineering Foundation through the Center for Field Responsive Molecules at Korea University and Samsung SDI. M.W.K. acknowledges partial support from DMR-0080034, IMT-2000-B3-2, KISTEP I-03-064 and Korea Health 21 R&D Project of Republic of Korea.
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Yoon, TY., Jeong, C., Lee, SW. et al. Topographic control of lipid-raft reconstitution in model membranes. Nature Mater 5, 281–285 (2006). https://doi.org/10.1038/nmat1618
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DOI: https://doi.org/10.1038/nmat1618
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