Thomas M. Weiss
Rice University
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Featured researches published by Thomas M. Weiss.
Biophysical Journal | 2001
Lin Yang; Thomas M. Weiss; Lai Ding; Huey W. Huang
Transmembrane pores induced by amphiphilic peptides, including melittin, are often modeled with the barrel-stave model after the alamethicin pore. We examine this assumption on melittin by using two methods, oriented circular dichroism (OCD) for detecting the orientation of melittin helix and neutron scattering for detecting transmembrane pores. OCD spectra of melittin were systematically measured. Melittin can orient either perpendicularly or parallel to a lipid bilayer, depending on the physical condition and the composition of the bilayer. Transmembrane pores were detected when the helices oriented perpendicularly to the plane of the bilayers, not when the helices oriented parallel to the bilayers. The evidence that led to the barrel-stave model for alamethicin and that to the toroidal model for magainin were reviewed. The properties of melittin pores are closely similar to that of magainin but unlike that of alamethicin. We conclude that, among naturally produced peptides that we have investigated, only alamethicin conforms to the barrel-stave model. Other peptides, including magainins, melittin and protegrins, all appear to induce transmembrane pores that conform to the toroidal model in which the lipid monolayer bends continuously through the pore so that the water core is lined by both the peptides and the lipid headgroups.
Biophysical Journal | 2000
Lin Yang; Thomas M. Weiss; Robert I. Lehrer; Huey W. Huang
Membrane pores spontaneously formed by antimicrobial peptides in membranes were crystallized for the first time by manipulating the sample hydration and temperature. Neutron diffraction shows that magainins and protegrins form stable pores in fully hydrated fluid membranes. At lower hydration levels or low temperature, the membrane multilayers crystallize. In one crystalline phase, the pores in each bilayer arrange in a regular hexagonal array and the bilayers are stacked into a hexagonal ABC lattice, corresponding to the cubic close-packed structure of spheres. In another crystalline phase, the bilayers are modulated into the rippled multilamellae, corresponding to a 2D monoclinic lattice. The phase diagrams are described. Crystallization of the membrane pores provides possibilities for diffraction studies that might provide useful information on the pore structures.
Biophysical Journal | 1999
William T. Heller; Thomas M. Weiss; Lin Yang; Huey W. Huang
Hydrophobic matching, in which transmembrane proteins cause the surrounding lipid bilayer to adjust its hydrocarbon thickness to match the length of the hydrophobic surface of the protein, is a commonly accepted idea in membrane biophysics. To test this idea, gramicidin (gD) was embedded in 1, 2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and 1, 2-myristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at the peptide/lipid molar ratio of 1:10. Circular dichroism (CD) was measured to ensure that the gramicidin was in the beta6.3 helix form. The bilayer thickness (the phosphate-to-phosphate distance, or PtP) was measured by x-ray lamellar diffraction. In the Lalpha phase near full hydration, PtP is 30.8 A for pure DLPC, 32.1 A for the DLPC/gD mixture, 35.3 A for pure DMPC, and 32.7 A for the DMPC/gD mixture. Gramicidin apparently stretches DLPC and thins DMPC toward a common thickness as expected by hydrophobic matching. Concurrently, gramicidin-gramicidin correlations were measured by x-ray in-plane scattering. In the fluid phase, the gramicidin-gramicidin nearest-neighbor separation is 26.8 A in DLPC, but shortens to 23.3 A in DMPC. These experiments confirm the conjecture that when proteins are embedded in a membrane, hydrophobic matching creates a strain field in the lipid bilayer that in turn gives rise to a membrane-mediated attractive potential between proteins.
Biophysical Journal | 2003
Thomas M. Weiss; Patrick C.A. van der Wel; J. Antoinette Killian; Roger E. Koeppe; Huey W. Huang
alpha-Helical transmembrane peptides, named WALP, with a hydrophobic sequence of leucine and alanine of varying length bordered at both ends by two tryptophans as membrane anchors, were synthesized to study the effect of hydrophobic matching in lipid bilayers. WALPs of 13-, 16-, and 19-residues were incorporated into 1,2-dilauroyl-sn-glycero-3-phosphocholine (12C), 1,2-tridecanoyl-sn-glycero-3-phosphocholine (13C), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (14C) bilayers in the form of oriented multilayers. Oriented circular dichroism spectra and x-ray diffraction patterns showed that the peptides were homogenously distributed in the lipid bilayers with the helical axes oriented approximately normal to the plane of bilayers. But in all cases, x-ray diffraction showed that the peptides did not alter the thickness of the bilayer. This is contrary to the case of gramicidin where 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dilauroyl-sn-glycero-3-phosphocholine clearly thinned and thickened, respectively, to approach the hydrophobic thickness of the gramicidin channels. The result seems to indicate that the packing of lipid chains around a single helix is fundamentally different from the way the chains pack against a large protein surface.
Biophysical Journal | 1999
William T. Heller; Thomas M. Weiss; Lin Yang; Huey W. Huang
We present a quantitative analysis of the effects of hydrophobic matching and membrane-mediated protein-protein interactions exhibited by gramicidin embedded in dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC) bilayers (Harroun et al., 1999. Biophys. J. 76:937-945). Incorporating gramicidin, at 1:10 peptide/lipid molar ratio, decreases the phosphate-to-phosphate (PtP) peak separation in the DMPC bilayer from 35.3 A without gramicidin to 32.7 A. In contrast, the same molar ratio of gramicidin in DLPC increases the PtP from 30.8 A to 32.1 A. Concurrently, x-ray in-plane scattering showed that the most probable nearest-neighbor separation between gramicidin channels was 26.8 A in DLPC, but reduced to 23.3 A in DMPC. In this paper we review the idea of hydrophobic matching in which the lipid bilayer deforms to match the hydrophobic surface of the embedded proteins. We use a simple elasticity theory, including thickness compression, tension, and splay terms to describe the membrane deformation. The energy of membrane deformation is compared with the energy cost of hydrophobic mismatch. We discuss the boundary conditions between a gramicidin channel and the lipid bilayer. We used a numerical method to solve the problem of membrane deformation profile in the presence of a high density of gramicidin channels and ran computer simulations of 81 gramicidin channels to find the equilibrium distributions of the channels in the plane of the bilayer. The simulations contain four parameters: bilayer thickness compressibility 1/B, bilayer bending rigidity Kc, the channel-bilayer mismatch Do, and the slope of the interface at the lipid-protein boundary s. B, Kc, and Do were experimentally measured; the only free parameter is s. The value of s is determined by the requirement that the theory produces the experimental values of bilayer thinning by gramicidin and the shift in the peak position of the in-plane scattering due to membrane-mediated channel-channel interactions. We show that both hydrophobic matching and membrane-mediated interactions can be understood by the simple elasticity theory.
Biochemistry | 2003
Lai Ding; Lin Yang; Thomas M. Weiss; Alan J. Waring; Robert I. Lehrer; Huey W. Huang
We study the interaction of antimicrobial peptides with lipopolysaccharide (LPS) bilayers to understand how antimicrobial peptides interact with the LPS monolayer on the outer membrane of Gram-negative bacteria. LPS in water spontaneously forms a multilamellar structure composed of symmetric bilayers. We performed X-ray lamellar diffraction and wide-angle in-plane scattering to study the physical characteristics of LPS multilayers. The multilayer alignment of LPS is comparable to phospholipids. Thus, it is suitable for the application of oriented circular dichroism (OCD) to study the state of peptides in LPS bilayers. At high hydration levels, the chain melting temperature in multilamella detected by X-ray diffraction is the same as that of LPS aqueous dispersions, as measured by calorimetry. LPS has a strong CD, but with a careful subtraction of the lipid background, the OCD of peptides in LPS is measurable. The method was tested successfully with melittin. It was then applied to two representative antimicrobial peptides, magainin and protegrin. At peptide concentrations comparable to the physiological conditions, both peptides penetrate transmembrane in LPS bilayers. The results imply that antimicrobial peptides readily penetrate the LPS monolayer of the outer membrane.
Biophysical Journal | 1998
Lin Yang; William T. Heller; Thomas M. Weiss; Huey W. Huang
We describe a method of measuring neutron scattering of aligned membranes with the momentum transfer oriented parallel or partly perpendicular to the plane of the membranes. The method obtains the complete information for the structures within fluid membranes obtainable by scattering. Data from alamethicin- and magainin-induced pores are presented. Although the in-plane scattering curves of these two peptides are similar to each other, their off-plane scattering patterns are strikingly distinct. Magainin pores exhibit intermembrane correlations.
Biophysical Journal | 1999
Lin Yang; Thomas M. Weiss; William T. Heller; Huey W. Huang
In a previous paper (Yang et al., Biophys. J. 75:641-645, 1998), we showed a simple, efficient method of recording the diffraction patterns of supramolecular peptide assemblies in membranes where the samples were prepared in the form of oriented multilayers. Here we develop a method of analysis based on the diffraction theory of two-dimensional liquids. Gramicidin was used as a prototype model because its pore structure in membrane in known. At full hydration, the diffraction patterns of alamethicin and magainin are similar to gramicidin except in the scale of q (the momentum transfer of scattering), clearly indicating that both alamethicin and magainin form pores in membranes but of different sizes. When the hydration of the multilayer samples was decreased while the bilayers were still fluid, the in-plane positions of the membrane pores became correlated from one bilayer to the next. We believe that this is a new manifestation of the hydration force. The effect is most prominent in magainin patterns, which are used to demonstrate the method of analysis. When magainin samples were further dehydrated or cooled, the liquid-like diffraction turned into crystal-like patterns. This discovery points to the possibility of investigating the supramolecular structures with high-order diffraction.
Biophysical Journal | 2003
Thomas M. Weiss; Poe-Jou Chen; Harald Sinn; E. Ercan Alp; Sow-Hsin Chen; Huey W. Huang
We investigated the application of inelastic x-ray scattering (IXS) to lipid bilayers. This technique directly measures the dynamic structure factor S(q,omega) which is the space-time Fourier transform of the electron density correlation function of the measured system. For a multiatomic system, the analysis of S(q,omega) is usually complicated. But for multiple bilayers of lipid, S(q,omega) is dominated by chain-chain correlations within individual bilayers. Thus IXS provides a unique probe for the collective dynamics of lipid chains in a bilayer that cannot be obtained by any other method. IXS of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylcholine + cholesterol at two different concentrations were measured. S(q,omega) was analyzed by three-mode hydrodynamic equations, including a thermal diffusive mode and two propagating acoustic modes. We obtained the dispersion curves for the phonons that represent the collective in-plane excitations of lipid chains. The effect of cholesterol on chain dynamics was detected. Our analysis shows the importance of having a high instrument resolution as well as the requirement of sufficient signal-to-noise ratio to obtain meaningful results from such an IXS experiment. The requirement on signal-to-noise also applies to molecular dynamics simulations.
Biophysical Chemistry | 2003
Poe-Jou Chen; Yun Liu; Thomas M. Weiss; Huey W. Huang; Harald Sinn; E. Ercan Alp; Ahmet Alatas; Ayman Said; Sow-Hsin Chen
We summarize a series of experimental results made with the newly developed high resolution X-ray scattering (IXS) instrument on two pure lipid bilayers, including dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC) in both gel and liquid crystal phases, and lipid bilayers containing cholesterol. By analyzing the IXS data based on the generalized three effective eigenmode model (GTEE), we obtain dispersion relations of the high frequency density oscillations (phonons) of lipid molecules in these bilayers. We then compare the dispersion relations of pure lipid bilayers of different chain lengths among themselves and the dispersion relations of pure lipid bilayers with those of the cholesterol containing bilayers. We also compare our experimental results with collective dynamics data generated by computer molecular dynamics (MD) simulations for dipalmitoylphosphatidylcholine (DPPC) in gel phase and DMPC in liquid crystal phase.