98 / 120
Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
93
62-POS
Board 31
Line Tension at Lipid Phase Boundaries as Driving Force for HIV Fusion Peptide-
Mediated Membrane Fusion
Sung-Tae Yang
, Volker Kiessling, Lukas K. Tamm.
University of Virginia, Charlottesville, VA, USA.
Lipids and proteins are organized in cellular membranes in clusters, often called “lipid rafts”.
Although raft-constituent ordered lipid domains are thought to be energetically unfavorable for
membrane fusion, rafts have long been implicated in many biological fusion processes. For the
case of HIV gp41-mediated membrane fusion, this apparent contradiction can be resolved by
recognizing that the interfaces between ordered and disordered lipid domains are the
predominant sites of fusion. Here we show that line tension at lipid domain boundaries
contributes significant energy to drive gp41 fusion peptide-mediated fusion. This energy, which
depends on the hydrophobic mismatch between ordered and disordered lipid domains, may
contribute tens of kBT to fusion, i.e., it is comparable to the energy required to form a lipid stalk
intermediate. Line-active compounds such as vitamin E lower line tension in inhomogeneous
membranes, thereby inhibit membrane fusion, and thus may be useful natural viral entry
inhibitors.
65-POS
Board 33
Determining the Specificity of Insoluble Protein Trans-Membrane Domains to Lipid
Compositions
Roy Ziblat
1
, Laura Arriaga
2
, Shaorong Chong
3
, David Weitz
1
.
1
Harvard University, Cambridge, MA, USA,
2
Complutense University of Madrid, Madrid, Spain,
3
New England Biolabs, Ipswich, MA, USA.
The specific interactions between proteins and lipid compositions are a key feature in the
architecture and function of biological membranes. However, most proteins interacting with
lipids are insoluble in water. Therefore, studying their specificity to lipids is very challenging,
especially when focusing on their trans-membrane domains that span through the hydrophobic
membrane. We introduce here a method that overcomes the solubility limitation and identifies
the specific binding of trans-membrane domains to a membrane library composed of over a
hundred different lipid compositions. This study reveals that trans-membrane domains are highly
selective and that the specific interactions of trans-membrane domains to lipids depend not only
on the presence of a single lipid, but on a combination of a few. Comparison of five human trans-
membrane domains indicates that each has a unique affinity profile, demonstrating the
complexities of protein-lipids interactions and indicating the importance of studying the
specificity of trans-membrane domains to lipids.