Effect of Alcohols on Lipid Bilayer Rigidity, Stability, and Area/Molecule
(in collaboration with David Block and Roland Faller )

Hung van Ly (Ph.D. Chemical Engineering, U C Davis 2003)
Kara Tierney (graduate student, chemical engineering)

Recent Project Progress:
We used micropipette aspiration to directly measure area compressibility modulus, bending modulus, lysis tension, lysis strain, and area expansion of fluid phase 1-stearoyl, 2-oleoyl phosphatidylcholine (SOPC) lipid bilayers exposed to aqueous solutions of short-chain alcohols at alcohol concentrations ranging from 0.1 M to molar.  The order of effectiveness in decreasing mechanical properties and increasing area per molecule was butanol>propanol>ethanol>methanol although the lysis strain was invariant to alcohol chain-length.  Quantitatively, the trend in area compressibility modulus follows Traube’s rule of interfacial tension reduction, i.e. for each additional alcohol CH2 group, the concentration required to reach the same area compressibility modulus was reduced roughly by a factor of three.  We convert our area compressibility data into interfacial tension to: confirm that Traube’s rule is followed for bilayers; show that alcohols decrease the interfacial tension of bilayer-water interfaces less effectively than oil-water interfaces; determine the partition coefficients and standard Gibbs adsorption energy per CH2 group for adsorption of alcohol into the lipid headgroup region; and predict the increase in area per headgroup as well as the critical radius and line tension of a membrane pore for each concentration and chain-length of alcohol.  The area expansion predictions were confirmed by direct measurements of the area expansion of vesicles exposed to flowing alcohol solutions.  These measurements were fitted to a membrane kinetic model to find membrane permeability coefficients of short-chain alcohols.  Taken together, the evidence presented here supports a view that alcohol partitioning into the bilayer headgroup region, with enhanced partitioning as the chain-length of the alcohol increases, results in chain-length dependent interfacial tension reduction with concomitant chain-length dependent reduction in mechanical moduli and membrane thickness. 

Project Publications:
“Interfacial Tension Effect of Ethanol on Lipid Bilayer Rigidity, Stability, and Area Expansion:  A Micropipette Aspiration Approach”, Langmuir, Ly, H. V., Block, D. E., and Longo, M. L., 2002, 18:8988 - 8995.
“The Influence of Short-Chain Alcohols on Interfacial Tension, Mechanical Properties, Area/Molecule, and Permeability of Fluid Lipid Bilayers”, Ly, H. V. and Longo, M. L., in press Biophysical Journal
“Probing the Interdigitated Phase of Gel Phase Lipid Bilayer (DPPC) by Micropipette Aspiration”, Ly, H. V. and Longo, M. L., in press

Methods and Some Results:
Micropipette Aspiration of Giant Unilamellar Vesicles
Bilayer mechanical properties (area compressibility modulus, bending modulus, lysis tension, and
lysis area strain) are determined by the well-established technique of micropipette aspiration of
single giant unilamellar vesicles.

Micropipette aspiration of a vesicle to demonstrate the increase (delta L) in projection length, L,
as the membrane tension, t, is adjusted from (a) 0.4 mN/m to (b) 2 mN/m.

 
Average area compressibility modulus values, KA (solid marks) and Kapp (open marks), of SOPC vesicles in alcohol/water mixtures. Symbols are methanol (diamonds), ethanol (squares), propanol (triangles), and butanol (circles). Values are based on 10 vesicles or more and bar indicates one standard deviation.  For clarity, only one representative error bar of all the measurements is shown (all error bars were equal or less than this one)


The Lipid Bilayer Follows Traube's Rule (equal spacing of 0.5 for all the curves).  Interfacial tension values vs. Log alcohol concentration for the four alcohol/water mixtures: methanol (diamonds), ethanol (squares), propanol (triangles), and butanol (circles). Values at the SOPC bilayer-water interface (solid marks) are from the KA/6 relation, and values at the alkane-water interface (open marks) are reprinted from Bartell et al. (1941) and Rivera et al. (2003).