Group of Jeremy J. Ramsden
Physics of Biological Systems
Molecular recognition and assembly
Introduction: the central role of
interfaces in biomolecular recognition
Processes occurring at the solid/liquid
interface are central to the functioning of cells and organisms. Our aim
is to resolve dynamic and structural details of the interaction of molecules
in solution with surfaces such as the bilayer lipid membrane, under well-characterized
conditions which closely mimic the in vivo environment. A particularly
powerful technique in this regard is optical waveguide lightmode spectroscopy
(OWLS). It uses light to probe interfacial processes in a totally non-invasive,
non-perturbative way, unlike most other techniques, and the molecules under
investigation do not require modification with radioactive, fluorescent
etc. labels. Membranes incorporating proteins can be built up on the surface
of an optical waveguide and their interactions with soluble proteins studied
directly in real time.
General literature
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Ramsden, J.J. Review of new experimental methods for investigating random
sequential adsorption. J. statist. Phys. 73 (1993) 853-877.
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Ramsden, J.J. Experimental methods for investigating protein adsorption
kinetics at surfaces. Q. Rev. Biophys. 27 (1994) 41-105.
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Ramsden, J.J. Puzzles and paradoxes in protein adsorption. Chem. Soc. Rev.
24 (1995) 73-78.
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Ramsden, J.J. Dynamics of protein adsorption at the solid/liquid interface.
Recent Res. Devel. Phys. Chem. 1 (1997) 133-142.
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Ramsden, J.J. Towards zero-perturbation methods for investigating biomolecular
interactions. Colloids Surfaces A 141 (1998) 287-294.
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Ramsden, J.J. Biospecific interaction analysis using integrated optics
techniques. In: Quantitative Analysis of Biospecific Interactions, P. Lundahl,
A. Lundqvist and E. Greijer (eds). Amsterdam: Harwood, (1998).
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Ramsden, J.J. Kinetics of protein adsorption. In: M. Malmsten, ed., Biopolymers
at Interfaces. New York: Dekker (1998).
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Ramsden, J.J. OWLS: a versatile technique for sensing with bioarrays. Chimia
53 (1999) 67-71.
This paper gives a succint overview of the technique of optical waveguide
lightmode spectroscopy (OWLS), which has been developed by the author at
the Biozentrum (Basel University) as a precision tool for investigating
the biophysical chemistry of solid/liquid interfaces. After reviewing the
fundamentals of the technique, some applications are discussed: membrane
structure (including some previously unpublished work on the interaction
of mellitin with phospholipid bilayers), the interaction of cytochrome
P450 with lipid bilayer membranes, and the association of restriction enzymes
with DNA.
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Regulation of metabolism
A major area of activity focuses onto
understanding in molecular and submolecular detail the mechanisms responsible
for a large variety of regulatory functions involving interaction between
proteins and phospholipid bilayer membranes. This boils down to understanding
how the association of macromolecule A with B changes the affinity of A
for macromolecule C. B may be another macromolecule, a small ion or osmolyte,
or a surface. For investigating the role of surfaces, the Langmuir-Blodgett
technique is used to coat smooth planar optical waveguides with bilayer
membranes constituted from selected pure lipids and mixtures; a method
has also been perfected for reconstituting natural cell membranes onto
waveguides. Current topics include the role of Ca2+, other cofactors,
protein phosphorylation and lipid composition in controlling protein adsorption
and desorption; and the functional role of two dimensional clustering and
crystallization. Large scale numerical simulations are used to help analyze
the experimental results in detail.
Literature
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Ramsden, J.J. Calcium-dependence of laminin binding to phospholipid membranes.
Biopolymers 33 (1993) 475-477.
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Ramsden, J.J., Bachmanova, G.I. and Archakov, A.I. Kinetic evidence for
protein clustering at a surface. Phys. Rev. E. 50 (1994) 5072-5076.
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Ramsden, J.J. and Wright, C.S. The interaction between wheat germ agglutinin
and membrane incorporated glycophorin A. An optical binding study. Glycoconjugate
J. 12 (1995) 113-121.
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Vergères, G. and Ramsden, J.J. Binding of MARCKS-related protein
(MRP) to vesicular phospholipid membranes. Biochem. J. 330 (1998) 5-11.
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Michielin, O., Vergères, G. and Ramsden, J.J. Evidence for myristoylation-induced
compaction of MARCKS-related protein. J. Amer. Chem. Soc. 121 (1999) 6523-6526.
This paper addresses the interaction of MARCKS-related protein (MRP)
with lipid bilayers. By comparing the association and dissociation kinetics
of intact and unmyristoylated MRP to bilayers it is shown that the myristoyl
group not only contributes to the affinity for the membrane, but also induces
a conformational compactification (presumably to shield the myristoyl moiety
from unfavourable interactions with water) which allows the packing density
on the membrane surface to be doubled.
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Michielin, O., Ramsden, J.J. and Vergères, G. Unmyristoylated MARCKS-related
protein (MRP) binds to supported planar phosphatidylcholine membranes.
Biophys. Biochim. Acta 1375 (1998) 110-116.
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Ramsden, J.J. and Vergères, G. Nonelectrostatic contributions to
the binding of MARCKS-related protein to lipid bilayers. Arch. Biochem.
Biophys. 371 (1999) 241-245.
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J.J. Ramsden, On protein-lipid membrane interactions. Colloids Surfaces
B 14 (1999) 77-81.
The interfacial interaction energy is calculated for MARCKS-related
protein (MRP) and phospholipid bilayer membranes. The Lewis acid-base force
dominates under physiological conditions. The effector domain is a net
electron acceptor, and this, rather than its net positive electrostatic
charge, accounts for its attraction to lipid membranes, which are strong
net electron donors.
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Vergères, G. and Ramsden, J.J. Regulation of the binding of MARCKS-related
protein to lipid bilayer membranes by calmodulin. Arch. Biochem. Biophys.
378 (2000) 45-50.
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Protein adsorption and desorption
A vast number of technological and
biomedical processes revolve around adsorption (e.g. chromatography, filtration,
dialysis, storage of pharmaceuticals, biocompatibility of surgical implants).
We are devoting significant effort to the elucidation of the energy landscape
of adsorbing proteins and other biopolymers, which is the key to controlling
these processes.
OWLS represents a significant improvement
over existing techniques, e.g. tenfold greater sensitivity compared with
surface plasmon resonance (SPR) and ellipsometry. OWLS is also much more
versatile than SPR; in particular it can be readily used in conjunction
with all major biological environments, such as phospholipid bilayers,
basement membranes, DNA and polysaccharides.
Literature
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Ramsden, J.J. and Schneider, P. Membrane insertion and antibody recognition
of a glycosyl-phosphatidylinositol-anchored protein: an optical study.
Biochemistry 32 (1993) 523-529.
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Ramsden, J.J. Concentration scaling of protein deposition kinetics. Phys.
Rev. Lett. 71 (1993) 295-298.
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Kurrat, R., Ramsden, J.J. and Prenosil, J.E. Kinetic model for serum albumin
adsorption: experimental verification. J. chem. Soc. Faraday Trans. 90
(1994) 587--590.
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Ramsden, J.J. and Prenosil, J.E. The effect of ionic strength on protein
adsorption kinetics. J. phys. Chem. 98 (1994) 5376-5381.
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Ramsden, J.J. Report on the Second International Workshop on Random Sequential
Adsorption. Theory and Experiment. J. statist. Phys. 79 (1995) 491-496.
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Ramsden, J.J., Roush, D.J., Gill, D.S., Kurrat, R.G. and Willson R.C. Protein
adsorption kinetics drastically altered by repositioning a single charge.
J. Amer. chem. Soc. 117 (1995) 8511-8516.
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Kurrat, R., Prenosil, J.E. and Ramsden, J.J. Kinetics of human and bovine
serum albumin adsorption at silica-titania surfaces. J. Colloid Interface
Sci. 185 (1997) 1-8.
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Luthi, P.O., Ramsden, J.J. and Chopard, B. The role of diffusion in irreversible
deposition. Phys. Rev. E 55 (1997) 3111-3115.
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Ball, V. and Ramsden, J.J. Absence of surface exclusion in the first stage
of lysozyme adsorption is driven through electrostatic self-assembly. J.
phys. Chem. B 101 (1997) 5465-5469.
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Csúcs, G. and Ramsden, J.J. Generalized ballistic deposition of
small buoyant particles. J. chem. Phys. 109 (1998) 779-781.
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Guemouri, L. Ogier, J. and J.J. Ramsden, J.J. Optical properties of protein
monolayers during assembly. J. Ccem. Phys. 109 (1998) 3265-3268.
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P.R. Van Tassel, J.J. Ramsden, L. Guemouri, J. Talbot, G. Tarjus and P.
Viot. A particle-level model of irreversible protein adsorption with a
postadsorption transition. J. Colloid Interface Sci. 207 (1998) 317-323.
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Kurrat, R., Wälivaara, B., Marti, A., Textor, M., Tengvall, P., Ramsden,
J.J. and Spencer, N.D. Plasma protein adsorption on titanium. Colloids
Surfaces B 11 (1998) 187-201.
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Ball, V., Lustig, A. and Ramsden, J.J. Lag phases in the adsorption of
lysozyme to silica-titania surfaces in the presence of sodium thiocyanate.
Part I. Phenomenology. PCCP 1 (1999) 3667-3671.
This report describes the very unusual phenomenon of sigmoidal evolution
of protein adsorption at the solid/liquid interface in the presence of
sodium thiocyanate. A preliminary interpretation in terms of the nucleation
of lysozyme clusters is given.
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Bilayer lipid membrane structure
Changes in anisotropy, thickness and
packing density in supported planar phospholipid bilayers can be monitored
with high precision and excellent time resolution using OWLS. We have been
using it to study the interaction of small organic molecules (drugs) and
oligopeptides (hormones). Apart from the high sensitivity, a particular
advantage is that with this technique, the reversibility of the interactions
can be directly investigated. This is rather difficult to do, and is usually
not done, with spectroscopic or microcalorimetric investigations of these
interactions with the membranes in vesicular form, but unless reversibility
is established, the validity of results from the experiments with vesicles
remains questionable.
Literature
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Ramsden, J.J. Partial molar volume of solutes in bilayer lipid membranes.
J. phys. Chem. 97 (1993) 4479-4483.
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Ramsden, J.J. Partition coefficients of drugs in bilayer lipid membranes.
Experientia 49 (1993) 688-692.
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Meier, W. and Ramsden, J.J. Surface pressure determines the interaction
between poly(oxyethylene) and a surfactant bilayer. J. phys. Chem. 100
(1996) 1435-1438.
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Csúcs, G. and Ramsden, J.J. Interaction of phospholipid vesicles
with smooth metal oxide surfaces. Biophys. Biochim. Acta 1369 (1998) 61-70.
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Csúcs, G. and Ramsden, J.J. Solubilization of planar bilayers with
detergent. Biophys. Biochim. Acta 1369 (1998) 304-308.
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Ramsden, J.J. Molecular orientation in lipid bilayers. Phil. Mag. B 79
(1999) 381-386.
The article describes measurements of the birefringence of phospholipid
bilayers of different alkyl chain lengths. All showed positive birefringence.
This is inconsistent with the commonly depicted laminar structure of such
membranes, and shows that the predominant orientation of the lipid molecules
is perpendicular to the plane of the membrane. Implications for the permeability
of the membrane to small hydrophilic or amphiphilic molecules are discussed.
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Attachment, growth and spreading
of living cells
OWLS has been developed for measuring
the rate and hence the energetics of attachment of cells to surfaces in
situ. Furthermore, the technique enables the kinetics of morphological
change of attached cells to be monitored continuously in situ. This
is currently being exploited in collaboration with the Laboratory for Surface
Sience and Technology of the ETH, Zurich, to investigate the response of
cells to environmental stress, and to develop a new kind of toxicological
sensor.
Literature
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Ramsden, J.J., Li, S.-Y., Heinzle, E. and Prenosil, J.E. Kinetics of adhesion
and spreading of animal cells. Biotechnology and Bioengineering. 43 (1994)
939-945.
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Li, S.-Y., Ramsden, J.J., Prenosil, J.E. and Heinzle, E. Measurement of
adhesion and spreading kinetics of baby hamster kidney and hybridoma cells
using an integrated optical method. Biotechnology Prog. 10 (1994) 520-524.
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Ramsden, J.J., Li, S.-Y., Heinzle, E. and Prenosil, J.E. An optical method
for the measurement of number and shape of attached cells in real time.
Cytometry 19 (1995) 97-102.
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Chemical and biochemical sensors
A grating coupler incorporated into
an optical waveguide is an efficient transducer for converting a (bio)chemical
signal into an optical or electrical one. The application of these devices
as miniature sensors is being explored. Their excellent compatibility with
biological materials makes them promising candidates for in vivo
probes of metabolic processes. In addition, fundamental work on the parameters
governing the ultimate attainable sensitivity of this type of sensor is
being undertaken.
Literature
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Ramsden, J.J. Sensitivity enhancement of integrated-optics sensors using
Langmuir-Blodgett lipid films. Sensors Actuators B 15-16 (1993) 439-442.
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Saini, S., Kurrat, R., Prenosil, J.E. and Ramsden, J.J. Temperature dependence
of pyrolyzed sol-gel planar waveguide parameters. J. Phys D: Appl. Phys.
27 (1994) 1134-1138.
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Ramsden, J.J. Porosity of pyrolyzed sol--gel waveguides. J. mater. Chem.
4 (1994) 1263-1265.
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Ramsden, J.J., Bachmanova, G.I. and Archakov, A.I. Immobilization of proteins
to lipid bilayers. Biosensors and Bioelectronics 11 (1996) 523-528.
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Ramsden, J.J. A dosimeter for oligopeptide hormones. Sensors Actuators
B 30 (1996) 107-110.
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Ramsden, J.J. and Karrasch, S. Activated Langmuir-Blodgett films for immobilizing
proteins on planar surfaces. Sensors and Materials 8 (1996) 469-476.
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Goutev, N., Nickolov, Zh.S. and Ramsden, J.J. Waveguide Raman spectroscopy
of silica-titania thin films with grating coupling. J. Raman Spectroscopy
27 (1996) 897-900.
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Ramsden, J.J., Németh-Sallay, M., Vörös, J. and Szendrö,
I. Integrált optikai hullámvezetö szenzor felületi
adszorbció viszgálatára. Fizikai Szemle (1997) 281-285.
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Ramsden, J.J. Optical Biosensors. J. molec. Recognition 10 (1997) 109-120.
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Kurrat, R., Textor, M., Ramsden, J.J., Boeni, P. and Spencer, N.D. Instrumental
improvements in optical waveguide lightmode spectroscopy for the study
of biomolecule adsorption. Rev. sci. Instrum. 68 (1997) 2172-2176.
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Brynda, E., Houska, M., Skvor, J. and Ramsden, J.J. Immobilization of multilayer
bioreceptor assemblies on solid substrates. Biosensors Bioelectronics 13
(1998) 165-172.
Ramsden, J.J. Biomimetic protein immobilization using lipid bilayers. Biosensors
Bioelectronics 13 (1998) 593-598.
Ramsden, J.J. A sum parameter sensor for water quality. Water Research
33 (1999) 1147-1150.
This report describes the application of OWLS to the measurement of
impurities in water. The water to be tested is brought into contact with
a coated optical waveguide. Depending on the coating, different components
in the water (humus, viruses, organic pollutants, metal ions, etc.) interact
with the waveguide and cause a measurable response.
Nanotechnology
Spontaneous ordered assembly (sometimes
called self-assembly) of complex molecules at the solid/liquid interface
is the basis of a highly promising novel concept in materials and device
engineering. The ultimate goal is the development of low-cost, robust routes
to fabricating complex systems. Even the protagonists of this approach
admit that present knowledge of the processes involved is extremely rudimentary,
however. In collaboration with E.C. Constable (Institute of Inorganic Chemistry,
Basel University), we are investigating structures spontaneously formed
when large organometallic complexes are brought into contact with a solid/liquid
interface. Presently, we are exploring which control parameters are important
for determining the appearance of particular structures.
Literature
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Ramsden, J.J., Lvov, Yu.A. and Decher, G. Optical and X-ray structural
monitoring of molecular films assembled via alternate polyion adsorption.
Thin solid Films 254 (1995) 246-251.
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Constable, E.C., Harverson, P. and Ramsden, J.J. Adsorption of ruthenadendrimers
to silica-titania surfaces studied by optical waveguide lightmode spectroscopy
(OWLS). J. Chem. Soc. Chem. Comm. (1997) 1683-1684.
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Máté, M. and Ramsden, J.J. Colloidal particles efficiently
scavenge fatty acid Langmuir-Blodgett films. J. Dispersion Sci. Tech. (in
press).
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Ramsden, J.J. and Máté, M. Kinetics of monolayer particle
deposition. J. chem. Soc. Faraday Trans. 94 (1998) 783-788.
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Máté, M. and Ramsden, J.J. Addition of particles of alternating
charge. J. chem. Soc. Faraday Trans. 94 (1998) 287-294.
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Máté, M., Fendler, J.H., Ramsden, J.J., Szalma, J. and Hórvölgyi,
Z. Eliminating surface pressure gradient effects in contact angle determination
of nano- and microparticles using a film balance. Langmuir 14 (1998) 6501-6504.
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Development, evolution and related
topics
Literature
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Luthi, P.O., Preiss, A., Chopard, B. and Ramsden, J.J. A cellular automaton
model for neurogenesis in Drosophila. Physica D 118 (1998) 151--160.
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Dér, A and Ramsden, J.J. Evidence for loosening of a protein mechanism.
Naturwissenschaften 85 (1998) 353-355.
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J.J. Ramsden and J. Vohradský. Zipf-like behavior in procaryotic
protein expression. Phys. Rev. E 58 (1998) 7777-7780.
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Foundations and history of biophysical
chemistry
Literature
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J.J. Ramsden. Paracelsus-concept and realization. Interaction 3 (in press).
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J.J. Ramsden. Biophysical Chemistry. In: Encyclopaedia of Chemical Physics
and Physical Chemistry, J.H. Moore and N.D.Spencer, eds. Philadelphia:
IOP. (in press).
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Recent publications in other areas
of biophysical chemistry
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Vergères, G., Ramsden, J.J. and Waskell, L. The carboxyl terminus
of the membrane-binding domain of cytochrome b5 spans the bilayer of the
endoplasmic reticulum. J. biol. Chem. 270 (1995) 3414-3422.
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Ramsden, J.J. and Dreier, J. Kinetics of the interaction between DNA and
the type IC restriction enzyme StyR124/3I. Biochemistry 35 (1996) 3746-3753.
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M.G. Cacace, E.M. Landau and J.J. Ramsden. The Hofmeister series: salt
and solvent effects on interfacial phenomena. Q. Rev. Biophys. 30 (1997)
241-278.
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Ball, V. and Ramsden, J.J. Influence of D(-) and L(+) tartaric acid on
lysozyme
adsorption onto a silica-titania surface. Naturwissenschaften 85 (1998)
87-89.
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Ball, V. and Ramsden, J.J. Buffer dependence of refractive index increments
of protein solutions. Biopolymers 46 (1998) 489-492.
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Cs. Nemes, N. Rozlosnik and J.J. Ramsden, Direct measurement of the viscoelasticity
of adsorbed protein layers using atomic force microscopy. Phys. Rev. E
60 (1999) 1166-1169.
Scanning force microscopy is used to determine viscoelastic parameters
of massed adsorpta of lysozyme. The aqueous medium bathing the protein
layer is varied according to the Hofmeister series, with concomitant changes
in the surface properties and stability of the protein molecules.
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Last updated 1 December 2000