Membrane tethering and hemifusion-open questions and speculations from anonymous dreamers

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I have been talking to many people at the Liposomes, Exosomes, and Virosomes meeting in Ascona, Switzerland. One question I asked was about the topic of membrane tethering and fusion that was discussed during the lectures from Reinhard Jahn, Wolfhard Almers, Chris Stroupe, and Nikhil Gandasi. Beautiful images of bilayer interactions were shown that followed a step where the membranes engage in hemifusion. After that step, the stalk is created, followed by membrane fusion, where the bilayer is connected for the two cells/liposomes/etc.

I encouraged people to talk about what is known and what is not known, what is dreamed and speculated about this. These are my observations from those conversations:

Our theoretical colleagues have made some progress in this regard. These events have been simulated and described by Marrink and published in a beautiful publication over 13 years ago.

Their work suggests that the a single phospholipid undergoes a very unfavorable, rare event of flipping one acyl chain to the other bilayer, creating a high energy state that then may promote the flipping of one acyl chain of another lipid. Once two lipids flipped, the following steps in the process may happen in a more energetically favored way. Of course, right now there is no way to experimentally test this (at least as far as I heard here). However, from my conversations with people willing to share their knowledge, I heard that there are indeed some lipids in cell membranes that may be more prone to this rare behavior.  These lipids may be rare, like the ladderenes shown by Steve Boxer, or they are around our membranes but we haven’t really identified them.

A lot of the studies described during this conference lead us to conclude that many of our observations and the biology behind our studies depends on the context.

Liposomes, Exosomes and Virosomes Playlists and song suggestions wanted for the Thursday Dance

The meeting organizers have asked us bloggers to ask the biophysical community to send song requests (specific) or playlists to use during the party we will have after Thursday’s night lecture.

https://www.dpag.ox.ac.uk/team/matthew-wood

Send your ideas by Wednesday midnight EDT.

Thanks! Marina and Andrea

 

Liposomes, exosomes and virosomes. Learning lots in a beautiful place.

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photo credit: Luca Monticelli

 

Day 1 –September 12, 2016 (starting with yesterday’s evening lecture) has covered a wide variety of questions and approaches). I have highlighted some of the things shared by the speakers.

Steve Boxer made us all think late in the day about some of the weirdest molecules I have seen: ladderenes and their surprisingly lipid like properties.

Kalina Histrova proposed a new paradigm for Tyrosine kinase receptor signaling using intrinsic FRET in plasma membrane vesicles from apoptotic cells to determine that ligand binding is not required for dimerization but increases the activation.

Dimitrios Stamou showed the heterogeneity of vesicles with proton transporters at the single vesicle level, where one transporter function is observed with bulk fluorescence inside the vesicle.

Kirsten Bacia showed the COPII vesicles and tubules in GTP non-hydrolyzing and  hydrolyzing conditions and reminded us that the way we define synthetic membranes depends on the context of our work.

Shirley Schreier illustrated the differences between the interactions between micelles and bilayers and the specificity that bilayers have for the type of lipids within it.

Helen Saibil showed us that pore forming proteins could be deadly yet beautiful like flowers and that the key to the conformational change may not be in the place where the change is happening.

Don Engelman walked us through a biophysics to bedside transmembrane peptide that pHLIPs and has the potential for imaging and drug deliver

Philippe Bastiens gave us the philosophical perspective of interdependence and recursion by comparing the interdependence of receptors (EphR and EGFR) with opposite functions (activation or inhibition of Erk and AKT). A big lesson of asking the question that gives you an answer that changes the question.

Jean-Marie Ruysschaert showed us how to turn ‘a mistake’ into the amazing discovery of how a cationic lipid can activate Toll like receptor-4 and the biochemical basis of this lipid activation. Moreover, he proposes that TLRs are the Swiss army knife of immunity, activated by a variety of materials.

Marta Bally showed her studies on influenza virus A and C matrix protein 1 going over the structure of the domains, its binding to bilayers and giant unilamellar vesicles and its ability to form protein rings without lipid.

Martin Hof presented an elegant and comprehensive study of the role of sphingomyelin and gangliosides on the formation of Alzheimer’s beta peptide oligomerization.

The discussion has been very engaging, with excellent questions. Andrea, my fellow thematic meetign blogger in Ascona,  presented during the Poster session today. It was a hot, humid afternoon and the several fans in the room were not enough, but nevertheless, the poster session interactions were quite lively.

 

-Marina Ramirez-Alvarado

Jet lagged but excited about the Liposome, exosome, and virosome thematic meeting

My fellow guest blogger, Andrea Catte did a fantastic job introducing himself and his career. Instead of telling you about myself; you can read my profile from Biophysics week.

 

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View of Ascona from the meeting hotel

I am very excited about this thematic meeting as I am relatively new in the exosome field. The program has an incredible list of speakers and the meeting is in a beautiful, remote location that will allow us to really get to know a lot of Biophysicists. I already met some very nice people at the Locarno train station, the shuttle drive, and at the remote hotel site. The manager drove me through the curvy, steep, roads on his jeep!

I left Rochester, MN on Saturday at 11:30 AM, Central Time. I arrived to Monte Verita, Ascona at 4:15 PM, central European Time. Andrea and I will share the highlights of the meeting throughout the week.

Marina Ramirez-Alvarado