Browsing by Author "Sun, Yen"

Now showing 1 - 6 of 6
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    Applying high-resolution filtering based on non-convex regularization of Radon Transform on seismic imaging
    (2018-06-28) Sun, Yen; Levander, Alan
    In this study we propose a novel high-resolution filtering method based on non-convex regularization of the Radon Transform and demonstrate several possible applications. The Radon transfer sums signals exhibiting linear, parabolic or hyperbolic moveout in the original domain (t-Δ domain) to a single event in the new domain (Radon domain). Consequently, in the Radon domain, the target signals can be isolated easily from some types of noise. A high-resolution Radon Transform can be achieved by applying least-square inversion in the frequency domain. To further enhance the spatial resolution in the Radon domain and decrease the computational cost, a pre-processing method was developed in our group (Aharchaou and Levander 2016) based on the linear Radon transform in the frequency domain implemented with compressive sensing theory. The compressive sensing approach helps recover the sparsest solutions in the Radon domain for underdetermined inverse problems. Instead of least square minimization, a non-convex minimization (Lp regularization with 0
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    Interaction of Daptomycin with Lipid Bilayers: A Lipid Extracting Effect
    (American Chemical Society, 2014) Chen, Yen-Fei; Sun, Tzu-Lin; Sun, Yen; Huang, Huey W.
    Daptomycin is the first approved member of a new structural class of antibiotics, the cyclic lipopeptides. The peptide interacts with the lipid matrix of cell membranes, inducing permeability of the membrane to ions, but its molecular mechanism has been a puzzle. Unlike the ubiquitous membrane-acting host-defense antimicrobial peptides, daptomycin does not induce pores in the cell membranes. Thus, how it affects the permeability of a membrane to ions is not clear. We studied its interaction with giant unilamellar vesicles (GUVs) and discovered a lipid-extracting phenomenon that correlates with the direct action of daptomycin on bacterial membranes observed in a recent fluorescence microscopy study. Lipid extraction occurred only when the GUV lipid composition included phosphatidylglycerol and in the presence of Ca2+ ions, the same condition found to be necessary for daptomycin to be effective against bacteria. Furthermore, it occurred only when the peptide/lipid ratio exceeded a threshold value, which could be the basis of the minimal inhibitory concentration of daptomycin. In this first publication on the lipid extracting effect, we characterize its dependence on ions and lipid compositions. We also discuss possibilities for connecting the lipid extracting effect to the antibacterial activity of daptomycin.
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    Membrane Permeability of Hydrocarbon-Cross-Linked Peptides
    (Biophysical Society, 2013-05) Sun, Tzu-Lin; Sun, Yen; Lee, Chang-Chun; Huang, Huey W.
    Schafmeister, Po, and Verdine (another study) introduced a method using a hydrocarbon linker (staple) to stabilize a peptide in a helical configuration. One intended goal of this scheme is to facilitate the delivery of peptide drugs into target cells. Here, we investigate whether stapled peptides are intrinsically membrane permeable, by performing a case study on a stapled 12-mer peptide named NYAD-1. We found that the native peptide CAI (an HIV-1 inhibitor) does not bind to lipid bilayers, however NYAD-1 indeed permeates through lipid bilayers even at low solution concentrations. To understand the reason for the membrane permeability, we investigated the physical properties of NYAD-1 as a function of bound peptide/lipid molar ratio P/L. We found that NYAD-1 spontaneously binds to a lipid bilayer. At low P/L, the peptide primarily binds on the polar-apolar interface with its helical axis parallel to the bilayer, which has the effect of stretching the membrane area and thinning the membrane. The membrane thinning reaches its maximum at P/L ~1/15-1/12 in DOPC bilayers. Additional bound peptides have little thinning effect and their helical axes are normal to the plane of bilayers. Thus, the stapled peptide has a membrane interaction behavior similar to helical antimicrobial peptides, such as magainin and melittin. We emphasize that not all peptides that bind to lipid bilayers in the a-helical form behave this way.
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    Methods of micro manipulating giant lipid vesicles for the studies of molecular interactions with membranes and membrane-membrane interactions
    (2011) Sun, Yen; Huang, Huey W.
    The lipid matrix of cell membranes is a natural binding site for amphipathic molecules. Consequently there are water-soluble, amphipathic peptides and proteins that exert their functions on membranes. Studies also showed that binding of amphipathic molecules (such as drugs) may change the functions of membrane proteins by altering the physical properties of the membrane. Thus, we want to understand how amphipathic molecules interact with membranes and find out the consequences of such membrane-molecule interactions. My thesis consists of development of new methods for studying the kinetics of molecular interactions with membranes and a series of comparative studies on different membrane-active molecules including peptides, proteins and drugs. My contribution to the methods for kinetics is to complement the equilibrium methods already developed in our lab for past twenty years. I established a micropipette aspiration system based on the system developed by Evan Evans in the 80's, but instead of measuring the elastic properties of membranes, we used it to study the dynamic interaction processes between amphipathic molecules and membranes.
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    Mode of Action of Antimicrobial Peptides on E. coli Spheroplasts
    (Cell Press, 2016) Sun, Yen; Sun, Tzu-Lin; Huang, Huey W.
    We investigated the phenomena of antimicrobial peptides (AMPs) directly attacking the cytoplasmic membranes of Escherichia coli spheroplasts. We developed a procedure for fluorescence recovery after photobleaching to examine dye leakage through bacterial membranes as AMPs in solution bound to the membranes. We found that the AMP binding did not increase the apparent membrane area of a spheroplast, contrary to the response of a lipid-bilayer vesicle, which always showed a membrane area expansion by AMP binding. The permeability through the bacterial membrane increased in a sigmoidal fashion as the AMP binding increased in time, exhibiting a cooperative behavior of AMPs. The analysis of fluorescence recovery after photobleaching showed that the fluxes of dye molecules into and out of the cell were consistent with diffusion of molecules through a number of pores that increased with binding of AMPs and then saturated to a steady level. We discovered a new, to our knowledge, experimental parameter called the flux rate that characterizes the AMP-induced permeability of dye molecules through bacterial membranes. The phenomena observed in bacterial membranes are consistent with the pore-forming activities of AMPs previously observed in lipid bilayers. The experimental value of the flux rate per pore is much smaller than a theoretical value that assumes no friction for the dye molecule’s permeation through the pore. We believe that experimental studies of the flux rate will be useful for further analysis of AMPs’ permeabilization mechanisms.
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    Why hydrocarbon-cross-linked peptides are membrane permeable
    (2012) Sun, Tzu-Lin; Lee, Chang-Chun; Sun, Yen; Huang, Huey W.