In situ and real-time sfg measurements revealing organization and transport of cholesterol analogue 6-ketocholestanol in a cell membrane
2014 (English)In: Journal of Physical Chemistry Letters, ISSN 1948-7185, Vol. 5, no 3, 419-424 p.Article in journal (Refereed) Published
Cholesterol organization and transport within a cell membrane are essential for human health and many cellular functions yet remain elusive so far. Using cholesterol analogue 6-ketocholestanol (6-KC) as a model, we have successfully exploited sum frequency generation vibrational spectroscopy (SFG-VS) to track the organization and transport of cholesterol in a membrane by combining achiral-sensitive ssp (ppp) and chiral-sensitive psp polarization measurements. It is found that 6-KC molecules are aligned at the outer leaflet of the DMPC lipid bilayer with a tilt angle of about 10. 6-KC organizes itself by forming an α-β structure at low 6-KC concentration and most likely a β-β structure at high 6-KC concentration. Among all proposed models, our results favor the so-called umbrella model with formation of a 6-KC cluster. Moreover, we have found that the long anticipated flip-flop motion of 6-KC in the membrane takes time to occur, at least much longer than previously thought. All of these interesting findings indicate that it is critical to explore in situ, real-time, and label-free methodologies to obtain a precise molecular description of cholesterol's behavior in membranes. This study represents the first application of SFG to reveal the cholesterol-lipid interaction mechanism at the molecular level.
Place, publisher, year, edition, pages
2014. Vol. 5, no 3, 419-424 p.
cellular organization and transport, cholesterol, flip-flop, label-free, molecular level, sum frequency generation
IdentifiersURN: urn:nbn:se:kth:diva-142802DOI: 10.1021/jz402537wISI: 000331153600004ScopusID: 2-s2.0-84893836465OAI: oai:DiVA.org:kth-142802DiVA: diva2:704721
QC 201403132014-03-132014-03-122014-03-21Bibliographically approved