Biomedical subjects

Robijn Bruinsma

Publications and source records attributed to Robijn Bruinsma.

11 recordsLinked to original sources

PubMed2006

Monte Carlo simulations of polyelectrolytes inside viral capsids.

Structural features of polyelectrolytes as single-stranded RNA or double-stranded DNA confined inside viral capsids and the thermodynamics of the encapsidation of the polyelectrolyte into the viral capsid have been examined for various polyelectrolyte lengths by using a coarse-grained model solved by Monte Carlo simulations. The capsid was modeled as a spherical shell with embedded charges and the genome as a linear jointed chain of oppositely charged beads, and their sizes corresponded to those of a scaled-down T=3 virus. Counterions were explicitly included, but no salt was added. The encapisdated chain was found to be predominantly located at the inner capsid surface, in a disordered manner for flexible chains and in a spool-like structure for stiff chains. The distribution of the small ions was strongly dependent on the polyelectrolyte-capsid charge ratio. The encapsidation enthalpy was negative and its magnitude decreased with increasing polyelectrolyte length, whereas the encapsidation entropy displayed a maximum when the capsid and polyelectrolyte had equal absolute charge. The encapsidation process remained thermodynamically favorable for genome charges ca. 3.5 times the capsid charge. The chain stiffness had only a relatively weak effect on the thermodynamics of the encapsidation.

Capsid↗

PubMed2005

Electrostatics and the assembly of an RNA virus.

Electrostatic interactions play a central role in the assembly of single-stranded RNA viruses. Under physiological conditions of salinity and acidity, virus capsid assembly requires the presence of genomic material that is oppositely charged to the core proteins. In this paper we apply basic polymer physics and statistical mechanics methods to the self-assembly of a synthetic virus encapsidating generic polyelectrolyte molecules. We find that (i) the mean concentration of the encapsidated polyelectrolyte material depends on the surface charge density, the radius of the capsid, and the linear charge density of the polymer but neither on the salt concentration nor the Kuhn length, and (ii) the total charge of the capsid interior is equal but opposite to that of the empty capsid, a form of charge reversal. Unlike natural viruses, synthetic viruses are predicted not to be under an osmotic swelling pressure. The design condition that self-assembly only produces filled capsids is shown to coincide with the condition that the capsid surface charge exceeds the desorption threshold of polymer surface adsorption. We compare our results with studies on the self-assembly of both synthetic and natural viruses.

Capsid↗

PubMed2005

Theory of force regulation by nascent adhesion sites.

The mechanical coupling of a cell with the extracellular matrix relies on adhesion sites, clusters of membrane-associated proteins that communicate forces generated along the F-Actin filaments of the cytoskeleton to connecting tissue. Nascent adhesion sites have been shown to regulate these forces in response to tissue rigidity. Force-regulation by substrate rigidity of adhesion sites with fixed area is not possible for stationary adhesion sites, according to elasticity theory. A simple model is presented to describe force regulation by dynamical adhesion sites.

Actins↗

PubMed2005

Helicoid to spiral ribbon transition.

We present a continuum description for the transition between the helicoid and spiral ribbon structures of chiral materials. At a critical value of the ratio between the bending and stretching moduli, the Föppl-von Kármán number, we encounter a continuous buckling transition from a straight helicoid to a spiral ribbon. Two of the three persistence lengths of the ribbon become very short at the transition point, indicating strong thermal shape fluctuations. The transition is discontinuous if the ribbon width is treated as a free thermodynamic variable.

Biopolymers↗

PubMed2005

Icosahedral packing of RNA viral genomes.

Many spherelike RNA viruses package a portion of their genome in a manner that mirrors the icosahedral symmetry of the protein container, or capsid. Graph-theoretical constraints forbid exact realization of icosahedral symmetry. This paper explores the consequences of graph-theoretical constraints on quasi-icosahedral genome structures. A key result is the prediction that the genome organization is a Hamiltonian path or cycle and that the associated assembly scenario of such single-stranded spherelike RNA viruses resembles that of cylindrical RNA viruses, such as tobacco mosaic viruses.

Capsid↗

PubMed2004

Physics of RecA-mediated homologous recognition.

To accomplish its DNA strand exchange activities, the Escherichia coli protein RecA polymerizes onto DNA to form a stiff helical nucleoprotein filament within which the DNA is extended by 50%. Homology search and recognition occurs between ssDNA within the filament and an external dsDNA molecule. We show that stretching the internal DNA greatly enhances homology recognition by increasing the probability that the homologous regions of a stretched DNA molecule and a parallel, unstretched DNA molecule will be "in register" at some position. We also show that the stretching and stiffness of the filament act together to ensure that initiation of homologous exchange between the substrate DNA molecules at one position precludes initiation of homologous exchange at any other position. This prevents formation of multiple exchange site "topological traps" which would prevent completion of the exchange reaction and resolution of the products.

Adenosine Triphosphatases↗

PubMed2003

Charge transfer, symmetry, and dissipation in donor-acceptor molecules.

We study charge transfer between donor-acceptor molecules subject to a mirror symmetry constraint in the presence of a dissipative environment. The symmetry requirement leads to the breakdown of the standard single reaction coordinate description, and to a new charge transfer model, in the limit of low temperature, based on two independent reaction coordinates of equal relevance. We discuss implications of these results to charge transfer between DNA base pairs, whose geometrical configuration is modified by the addition of the migrating charge in conformity with the discussed symmetry constraint.

DNA↗

PubMed2002

Mechanical force generation by G proteins.

GTP-hydrolyzing G proteins are molecular switches that play a critical role in cell signaling processes. Here we use molecular dynamics simulations to show that Ras, a monomeric G protein, can generate mechanical force upon hydrolysis. The generated force levels are comparable to those produced by ATP-hydrolyzing motor proteins, consistent with the structural similarities of the catalytic region of motor proteins and G proteins. The force transduction mechanism is based on an irreversible structural change, produced by the hydrolysis, which triggers thermal switching between force-generating substates through changes in the configurational space of the protein.

Computer Simulation↗

PubMed2002

Helfrich repulsion and dynamical phase separation of multicomponent lipid bilayers.

Thermal fluctuations of surfactant bilayers in an aqueous solution produce an effective, long-range repulsion that can lead to a continuous unbinding transition. We report on an optical interferometry study of the thermal fluctuations of multicomponent bilayers close to the unbinding transition. We find that, in contrast to the case of single-component bilayers, the thermal fluctuation spectrum of multicomponent bilayers does not agree with a continuous unbinding transition but instead indicates the proximity of an unbinding tricritical point.

Cholesterol↗

PubMed2002

Effects of torsional strain on thermal denaturation of DNA.

A class of simple statistical mechanical models for DNA melting, first proposed by Poland and Scheraga, has been demonstrated to exhibit a first or second order thermodynamic singularity, notwithstanding the intrinsic one-dimensional nature of the problem. In the present paper we consider the case of circular DNA and show that the inclusion of twist elastic energy in the Poland-Scheraga models leads either to suppression of the thermodynamic singularity or to a weak, third order singularity. Such behavior may also be present in linear DNA under mechanical influences that preclude the release of torsional strain.

Journal Article↗

PubMed2002

The nuclear pore complex mystery and anomalous diffusion in reversible gels.

The exchange of macromolecules between the cytoplasm and the nucleus of eukaryotic cells takes place through the nuclear pore complex (NPC), which contains a selective permeability barrier. Experiments on the physical properties of this barrier appear to be in conflict with current physical understanding of the rheology of reversible gels. This paper proposes that the NPC gel is anomalous and characterized by connectivity fluctuations. It develops a simplified model to demonstrate the possibility of enhanced diffusion constants of macromolecules trapped in such a gel.

Biological Transport, Active↗