Lipid bilayers: thermodynamics, structure, fluctuations, and interactions

Abstract

This article, adapted from our acceptance speech of the Avanti Award in Lipids at the 47th Biophysical Society meeting in San Antonio, 2003, summarizes over 30 years of research in the area of lipid bilayers. Beginning with a theoretical model of the phase transition (J.F.N.), we have proceeded experimentally using dilatometry and density centrifugation to study volume, differential scanning calorimetry to study heat capacity, and X-ray scattering techniques to study structure of lipid bilayers as a function of temperature. Electron density profiles of the gel and ripple phases have been obtained as well as profiles from several fluid phase lipids, which lead to many structural results that compliment molecular dynamics simulations from other groups. Using the theory of liquid crystallography plus oriented lipid samples, we are the first group to obtain both material parameters (KC and B) associated with the fluctuations in fluid phase lipids. This allows us to use fully hydrated lipid samples, as in vivo, to obtain the structure.

Fig. 1

Molecular volume (open circles) and heat capacity (solid line) vs. temperature for DPPC bilayers in excess water (Nagle and Wilkinson, 1982; Tristram-Nagle et al., 1987).

Fig. 2

Electron density profiles (EDPs) of gel phase (DPPC) and fluid phase (DOPC) bilayers (Tristram-Nagle et al., 1998).

Fig. 3

Summary of gel phase work showing low-angle data (left), wide-angle data from oriented sample (upper center), wide-angle data from unoriented MLVS (lower center), continuous Fourier transform (upper right), and electron density profile (lower right) showing three measures of bilayer thickness.

Fig. 4

Simulated EDPs of DOPC and the water contribution from Feller (unpublished). (A) Lamellar repeat spacing D = 63.1 Å corresponds to the fully hydrated DOPC bilayer structure from X-ray diffraction. Water spacing is D_W′ = 18.0 Å and water content is n_W = 32.8 water molecules per DOPC. (B) Lamellar repeat spacing D = 49.8 Å corresponds to 97% relative humidity (RH), water spacing D_W′ = 3.6 Å, and water content n_W = 14.5 (Tristram-Nagle et al., 1998). (C) Assuming no change in area from panel (B) gives a lamellar repeat spacing D = 45 Å for n_W = 9 with water spacing D_W′ < 0.

Fig. 5

EDPs obtained by MD simulation by Scott Feller (unpublished). Contributions from the various bilayer molecular components (Armen et al., 1998) are shown at right.

Fig. 6

Monte Carlo (MC) simulation of a stack of bilayers (Gouliaev and Nagle, 1998).

Fig. 7

High-resolution X-ray scattering data from MLVs, peak height normalized to the first order. Lost intensity is partially shown in gray.

Fig. 8

Two types of samples for X-ray diffraction: oriented samples of lipids on a solid substrate (left) and unoriented, “powder” samples of lipids in excess water in glass X-ray capillaries (right).

Fig. 9

Experimental geometry at CHESS using a flat silicon substrate and rotation motor.

Fig. 10

Physical setup at D1 station at CHESS.

Fig. 11

X-ray scattering data from a gel phase sample prepared on a mica substrate (DMPC at 10 °C). The beam is seen through a semi-transparent beam stop at the left.

Fig. 12

Diffuse scattering from fully hydrated, oriented DOPC. Positions of Bragg peaks are indicated by orders h.

Fig. 13

(A) The calculated structure factor S(q). (B) The form factor |F(q_z)|. (C) The intensity data. See text for labeled regions 1−4.

Fig. 14

|F(q_z)| of DOPC at 30 °C obtained from several samples at different hydration levels (diamonds) and from one fully hydrated sample (solid circles) (Lyatskaya et al., 2001).

Fig. 15

Electron density profile of DOPC at 30 °C constructed using the model fitting method and the X-ray intensity data from a fully hydrated, oriented sample (black line). For comparison is the DOPC profile constructed by Fourier construction using data from an unoriented sample (Tristram-Nagle et al., 1998) (gray). Also shown is the DOPC profile obtained by MD simulations by Scott Feller (black dots).