The relationship between permeant size and permeability in lipid bilayer membranes

Abstract

Permeability coefficients (Pm) across planar egg lecithin/decane bilayers and bulk hydrocarbon/water partition coefficients (Kw-->hc) have been measured for 24 solutes with molecular volumes, V, varying by a factor of 22 and Pm values varying by a factor of 10(7) to explore the chemical nature of the bilayer barrier and the effects of permeant size on permeability. A proper bulk solvent which correctly mimics the microenvironment of the barrier domain was sought. Changes in Pm/Kw-->hc were then ascribed to size-dependent partitioning and/or size-dependent diffusivity. The diffusion coefficient-size dependency was described by Dbarrier = Do/Vn. When n-decane was used as a reference solvent, the correlation between log Pm/Kw-->hc and log V was poor (r = 0.56) with most of the lipophilic (hydrophilic) permeants lying below (above) the regression line. Correlations improved significantly (r = 0.87 and 0.90, respectively) with more polarizable solvents, 1-hexadecene and 1,9-decadiene. Values of the size selectivity parameter n were sensitive to the reference solvent (n = 0.8 +/- 0.3, 1.2 +/- 0.1 and 1.4 +/- 0.2, respectively, for decane, hexadecene, and decadiene). Decadiene was selected as the most suitable reference solvent. The value for n in bilayer transport is higher than that for bulk diffusion in decane (n = 0.74 +/- 0.10), confirming the steep dependence of bilayer permeability on molecular size. Statistical mechanical theory recently developed by the authors suggests that a component of this steep size dependence may reside in size-dependent solute partitioning into the ordered chain region of bilayers. This theory, combined with the above diffusion model, yielded the relationship, Pm/Kw-->hc = D(o)exp(-alpha V)Vn. A fit of the experimental data to this model gave the best fit (r = 0.93) with alpha = 0.0053 +/- 0.0021 and n = 0.8 +/- 0.3, suggesting that both diffusion and partitioning mechanisms may play a role in determining the size dependence of lipid bilayer permeabilities.

Comparative studies on the effects of water, ethanol and water/ethanol mixtures on chemical partitioning into porcine stratum corneum and silastic membrane

“…The correlation of partitioning with molecular weight is, therefore, a reflection of the influence of molecular weight on lipophilicity and not due to a direct causal relationship between partitioning and molecular weight. This hypothesis is in agreement with previous studies showing that lipophilicity drives partitioning behavior in lipid bilayers (Xiang & Anderson 1994). It is also in agreement with the theorized influence of molecular size on partitioning behavior based on scaled-particle theory (Mitragotri et al 1999), which predicts that more energy is required for large molecules to partition into lipid bilayers.…”

pH determines the energetic efficiency of the cyanobacterial CO 2 concentrating mechanism

“…Here, k H2CO3 m = 3 × 10 −3 cm/s is the velocity of H 2 CO 3 permeation and 10 ðpK 1 −pHÞ is the ratio of H 2 CO 3 to HCO 3 − as a function of the pH and the first pK a of H 2 CO 3 (pK 1 ≈ 3.2Þ (22,31). This equation holds across the entire pH range considered here (6.5 ≤ pH ≤ 9; see SI Appendix for full derivation).…”

“…This implicit assumption is at odds with biochemical intuition that charge is a major determinant of membrane permeability (20). Indeed, the often-cited permeability coefficient of ≈ 3 × 10 −4 cm/s is representative of the uncharged H 2 CO 3 but three to four orders of magnitude too high for HCO 3 − and CO 3 2− (SI Appendix) (21,22). A recent model of the minimal CCM of Prochlorococcus MED4 made the inverse assumption: that the cell membrane is negligibly permeable to HCO 3 − , implicitly ignoring the rapid interconversion of HCO 3 − with the uncharged and highly permeable H 2 CO 3 (23).…”

Independence of substituent contributions to the transport of small-molecule permeants in lipid bilayer

“…This image illustrates that the sizes of the permeants explored in this study are sufficiently small that the entire permeant may be accommodated within the acyl chain region of the bilayer. Deuterium NMR order parameters indicate that about 72% of the chain segments in the bilayer interior lie within the highly ordered chain regions (13), which we have previously argued constitute the barrier domains located within each of the two halves of the bilayer (7,14). It appears that the length of pmethylhippuric acid is comparable to the thickness of these barrier regions.…”