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Biomedical subjects

W Sung

Publications and source records attributed to W Sung.

At least 19 recordsLinked to original sources
PubMed2001

Barrier crossing of a semiflexible ring polymer.

Motivated by the dynamics of a membrane in response to an external force, we study the thermally activated crossing of a semiflexible ring polymer over a potential barrier. For the bistable potential of Kramers type smoothly varying over a long length scale, we calculate the crossing rate using the multidimensional Kramers' rate theory and the functional integral method. We find that, due to its conformational fluctuation, the rate for a flexible ring is much larger than that for a stiff ring. For a sufficiently long chain length or a sufficiently weak bending modulus, the ring undergoes a compact-stretch transition. The stretched conformation of the chain results in a decrease of the activation energy and so the further increase of the rate. This result implies that the soft matter conformational flexibility and adaptability facilitate the barrier crossing.

Journal Article↗
PubMed2001

Membrane curvature induced by polymer adsorption.

The phenomena resulting from interaction between polymers and membranes pose important problems for biological applications. Based on a scaling theory, we investigate the spontaneous curvature of a membrane induced by either flexible or semiflexible chain adsorption. Irrespective of chain stiffness, a weakly adsorbed polymer induces the membrane to bend away (to have a positive curvature) from the polymer mostly due to increase of the conformational entropy compared with that for a flat surface. On the other hand, a strongly adsorbed polymer induces the membrane to bend toward the polymer mostly due to decrease in the interaction energy, leading to a possibility of encapsulation of polymer by the membrane.

Adsorption↗
PubMed2001

Coil-to-stretch transition, kink formation, and efficient barrier crossing of a flexible chain.

We study the thermally activated barrier crossing of a linear, flexible chain (polymer) under the Kramers bistable potential using the multidimensional barrier crossing theory and the functional integral method. We find that above a critical chain length or below a critical chain spring constant the chain at the barrier top undergoes coil-to-stretch transition, resulting in the formation of a kink. The emergence of the kink mode renormalizes the activation energy to a smaller value so as to facilitate the barrier crossing. In addition to this, the larger fluctuation of the polymer in the unstable region of the potential (compared to that in the confining well) further reduces the free energy barrier, and greatly enhances the crossing rate of a flexible chain. We calculate analytically the crossing rates and confirm the results by numerical simulations. The polymer in barrier crossing thus reveals its conformational flexibility and adjustment to external forces as characteristic features of soft matter dynamics.

Journal Article↗
PubMed1999

Effects of nonequilibrium fluctuations on ionic transport through biomembranes.

We investigate the effects of nonequilibrium fluctuations on ionic transport through ion channels in membranes using the concept of localized ratchet. Due to the localization, the ionic population in the binding site can be enhanced or suppressed depending upon ionic potential and its fluctuations, affecting the gating kinetics of the channel. The localized dichotomic fluctuations of ionic potential are shown to give rise to a current reversal differing from the results of periodic ratchets. It is also found that strong correlations between binding energy and membrane potential fluctuations induce resonancelike behaviors in ionic current as the fluctuating rate varies.

Journal Article↗
PubMed1997

Dynamics of pore growth in membranes and membrane stability.

Pores can form and grow in biomembranes because of factors such as thermal fluctuation, transmembrane electrical potential, and cellular environment. We propose a new statistical physics model of the pore growth treated as a non-Markovian stochastic process, with a free energy barrier and memory friction from the membrane matrix treated as a quasi-two-dimensional viscoelastic and dielectric fluid continuum. On the basis of the modern theory of activated barrier crossing, an analytical expression for membrane lifetime and the phase diagram for membrane stability are obtained. The memory effect due to membrane viscoelasticity and the elasticity due to cytoskeletal network are found to induce sharp transitions to membrane stability against pore growth and compete with other factors to manifest rich dynamic transitions over the membrane lifetime.

Biophysical Phenomena↗
PubMed1994

Parathyroid hormone fragments may stimulate bone growth in ovariectomized rats by activating adenylyl cyclase.

PTH is regarded conventionally as a catabolic hormone that stimulates osteoclastic resorption of bone. However, it has been known since 1932 that intermittent pulses of PTH stimulate bone formation in animals and humans. PTH independently activates two signal mechanisms: one that stimulates adenylyl cyclase and one that stimulates protein kinase C (PKC). The goal of this study was to use the 3- to 5-month-old ovariectomized (OVX) rat model to determine which of the two signal mechanisms is responsible for the anabolic action of PTH on bone. OVX triggered a large loss of trabecular bone without significantly affecting the normal slow growth of cortical bone in the distal halves of the femora. Daily injections of human hPTH(1-34) fragment (1 nmol/100 g body weight), which stimulated both adenylyl cyclase and membrane-associated PKC activity in osteoblast-like ROS 17/2 rat osteosarcoma cells, stimulated the growth of both cortical and trabecular bone in the OVX rats. Daily injections of the same dose of hPTH(1-31), which stimulated adenylyl cyclase but not PKC in ROS 17/2 cells, stimulated trabecular bone growth in the OVX rats less effectively than hPTH(1-34), but it stimulated cortical bone growth as rapidly and as dramatically as hPTH(1-34). Injections of equimolar amounts of desamino-hPTH(1-34) [N-propionyl(2-3)hPTH-amide], which stimulated PKC as strongly as hPTH(1-34) in ROS 17/2 cells but had a drastically reduced ability to stimulate adenylyl cyclase, or injections of recombinant hPTH(8-84) which stimulated PKC only in the ROS 17/2 cells, did not stimulate cortical or trabecular bone growth in the OVX animals. Thus, cyclic AMP and cyclic AMP-dependent protein kinases may be the primary mediators of the anabolic action of intermittent pulses of PTH on bone in OVX rats.

Adenylyl Cyclases↗
PubMed1992

Structural elements of human parathyroid hormone and their possible relation to biological activities.

Human parathyroid hormone (hPTH) and several deletion analogues were examined for the presence of secondary structure using circular dichroism spectroscopy. The spectra of hPTH and the deletion analogues 8-84, 34-53, 53-84, 1-34, 13-34, 1-19, and 20-34, in neutral, aqueous buffer, gave no evidence for extensive secondary structure. An alpha-helical-like spectral contribution was found to arise from a region within peptide 13-34. This spectral contribution was speculated to arise from partial stability of a helix consisting of residues 17-29. Molecular dynamics simulations of peptide 1-34 suggested that this peptide tends to fold with a bend defined by residues 10-14, with the amino-terminal and carboxyl-terminal residues tending to be in more extended forms and the other residues in helical-like conformations. The addition of trifluoroethanol promoted the formation of alpha-helix, mainly in the 1-34 region. The putative helix comprised of residues 17-29 was stabilized by the addition of 10-20% TFE, while a second putative helix proximal to the amino terminus, and comprised of residues 3-11, was stabilized by slightly higher concentrations of TFE. An amphiphilic sequence was identified within the 20-34 fragment. The development of alpha-helix on binding this fragment, and other analogues containing this sequence, to palmitoyloleoylphosphatidylserine vesicles provided experimental evidence for the potential role of this amphiphilic sequence in binding to membranes or to a membrane receptor. The relationships between these alpha-helical regions in 1-34, either potentiated by trifluoroethanol or lipid vesicles, are discussed in terms of different receptor-binding regions within hPTH.

Amino Acid Sequence↗
PubMed1984

Synthesis of a human insulin gene. VII. Synthesis of preproinsulin-like human DNA, its cloning and expression in M13 bacteriophage.

A 74-bp DNA sequence coding for the pre sequence of human preproinsulin and containing EcoRI termini was synthesized by the chemical enzymatic method, joined with previously synthesized proinsulin DNA, and cloned in the M 13mp8 vector. A clone pNB82 -121 was identified by DNA sequence which confirmed the correct orientation of the pre sequence to the proinsulin DNA. The EcoRI site at the junction of pre- and proinsulin DNA was eliminated by removing a triplet ATT using a synthetic 19-mer primer. To simplify preproinsulin isolation and to study its expression in the M 13 system, a 25-bp affinity leader sequence coding for (glu)7 was inserted at the remaining EcoRI site; this put the preproinsulin DNA in a correct reading frame with the AUG initiation codon of beta-galactosidase. Preproinsulin was expressed under lac promoter control as analyzed by a radioimmunoassay (RIA) against C-peptide.

Base Sequence↗
PubMed1984

The human preproinsulin gene: synthesis, cloning, gene modification, and expression studies.

A 355 base pair (bp) DNA sequence coding for human preproinsulin has been assembled by joining a synthetic DNA leader sequence coding for 24 preregion amino acids to the previously synthesized DNA duplex of 277 bp constituting the sequence of BCA chain. It was next cloned in M13 mp8 single-stranded bacteriophage and subjected to site-specific mutagenesis and phase shifting to allow its inducible expression under lac operator control. An affinity leader sequence of 25 bp has been added in an attempt to facilitate purification of the preproinsulin.

Bacteriophages↗
PubMed1982

Synthesis of a human insulin gene. V. Enzymatic assembly, cloning and characterization of the human proinsulin DNA.

To form a 258-bp sequence coding for human proinsulin, 41 synthetic deoxyribo-oligonucleotide fragments of 11 to 15 nucleotides in length were assembled by enzymatic methods. The coding sequence is preceded by ATG and following by TGA for translation start and stop signals, and terminated in an EcoRI and a BamHI recognition sequence. The complete synthetic sequence was ligated to a plasmid and cloned in Escherichia coli. The cloned DNA was shown to have the correct human proinsulin coding sequence.

Base Sequence↗