Robijn Bruinsma

Cell Adhesion as Wetting Transition

Cell adhesion is controlled by a complex interplay of short range (lock-and-key) forces mediated by cell surface receptors, a phalanx of (short and long range) nonspecific (generic) interactions, and last but not least membrane elasticity. The physical basis of cell adhesion is explored by the design of simplified model systems, mimicking cell and tissue surfaces, enabling local measurements of cellular shape changes and adhesion forces by microinterferometry. Cell adhesion can be understood as first-order dewetting transition that results in the formation of adhesion plaques, such as focal adhesion sites of cells, which allow cell adhesion at astonishingly low receptor densities. The repeller molecules of the glycocalix play a key role for the control of the adhesion transition and the mechanical stability of the adhering cells by relaxing the strength of the binding forces. Stress fibers are postulated to be essential for the stabilization of adhesion domains against leverage through bending moments enforced by hydrodynamic shear forces.

Viral self-assembly as a thermodynamic process.

The protein shells, or capsids, of nearly all spherelike viruses adopt icosahedral symmetry. In the present Letter, we propose a statistical thermodynamic model for viral self-assembly. We find that icosahedral symmetry is not expected for viral capsids constructed from structurally identical protein subunits and that this symmetry requires (at least) two internal switching configurations of the protein. Our results indicate that icosahedral symmetry is not a generic consequence of free energy minimization but requires optimization of internal structural parameters of the capsid proteins.

Elasticity theory and shape transitions of viral shells

Recently, continuum elasticity theory has been applied to explain the shape transition of icosahedral viral capsids--single-protein-thick crystalline shells--from spherical to buckled or faceted as their radius increases through a critical value determined by the competition between stretching and bending energies of a closed two-dimensional (2D) elastic network. In the present work we generalize this approach to capsids with nonicosahedral symmetries, e.g., spherocylindrical and conical shells. One key additional physical ingredient is the role played by nonzero spontaneous curvature. Another is associated with the special way in which the energy of the 12 topologically required fivefold sites depends on the background local curvature of the shell in which they are embedded. Systematic evaluation of these contributions leads to a shape phase diagram in which transitions are observed from icosahedral to spherocylindrical capsids as a function of the ratio of stretching to bending energies and of the spontaneous curvature of the 2D protein network. We find that the transition from icosahedral to spherocylindrical symmetry is continuous or weakly first order near the onset of buckling, leading to extensive shape degeneracy. These results are discussed in the context of experimentally observed variations in the shapes of a variety of viral capsids.

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.

Structural polymorphism of the cytoskeleton: A model of linker-assisted filament aggregation

The phase behavior of charged rods in the presence of interrod linkers is studied theoretically as a model for the equilibrium behavior underlying the organization of actin filaments by linker proteins in the cytoskeleton. The presence of linkers in the solution modifies the effective interrod interaction and can lead to interfilament attraction. Depending on the composition and physical properties of the system, such as linker-binding energies, filaments will orient either perpendicular or parallel to each other, leading to network-like or bundled structures. We show that such a system can have one of three generic phase diagrams, one dominated by bundles, another by networks, and the third containing both bundle and network-like phases. The first two diagrams can be found over a wide range of interaction energies, whereas the third diagram occurs only for a narrow range. These results provide theoretical understanding of the classification of linker proteins as bundling proteins or crosslinking proteins. In addition, they suggest possible mechanisms by which the cell may control cytoskeletal morphology.

Chirality and Equilibrium Biopolymer Bundles

We use continuum theory to show that chirality is a key thermodynamic control parameter for the aggregation of biopolymers: chirality produces a stable disperse phase of hexagonal bundles under moderately poor solvent conditions, as has been observed in in vitro studies of F actin [O. Pelletier et al., Phys. Rev. Lett. 91, 148102 (2003)]. The large characteristic radius of these chiral bundles is not determined by a mysterious long-range molecular interaction but by in-plane shear elastic stresses generated by the interplay between a chiral torque and an unusual, but universal, nonlinear gauge term in the strain tensor of ordered chains that is imposed by rotational invariance.

Entropic crystal–crystal transitions of Brownian squares

When a monolayer of hard microscale square platelets, produced lithographically, is osmotically concentrated in a flat plane to raise the particle area fraction ϕA, an order–order transition occurs between a hexagonal rotator crystal and a rhombic crystal. Strikingly, phases having fourfold symmetry are not observed at any ϕA. The rhombic lattice angle α increases continuously with ϕA, as the system maximizes its total rotational and translational entropy. A cage model, based on packing rotationally swept squares, or “squaroids,” reasonably predicts the measured α(ϕA), indicating that rotational entropy and the square particle shape combine to produce the rhombic unit cell.

Propulsion of African trypanosomes is driven by bihelical waves with alternating chirality separated by kinks.

Trypanosoma brucei, a parasitic protist with a single flagellum, is the causative agent of African sleeping sickness. Propulsion of T. brucei was long believed to be by a drill-like, helical motion. Using millisecond differential interference-contrast microscopy and analyzing image sequences of cultured procyclic-form and bloodstream-form parasites, as well as bloodstream-form cells in infected mouse blood, we find that, instead, motility of T. brucei is by the propagation of kinks, separating left-handed and right-handed helical waves. Kink-driven motility, previously encountered in prokaryotes, permits T. brucei a helical propagation mechanism while avoiding the large viscous drag associated with a net rotation of the broad end of its tapering body. Our study demonstrates that millisecond differential interference-contrast microscopy can be a useful tool for uncovering important short-time features of microorganism locomotion.

Folding Langmuir monolayers.

The maximum pressure a two-dimensional surfactant monolayer is able to withstand is limited by the collapse instability towards formation of three-dimensional material. We propose a new description for reversible collapse based on a mathematical analogy between the formation of folds in surfactant monolayers and the formation of Griffith Cracks in solid plates under stress. The description, which is tested in a combined microscopy and rheology study of the collapse of a single-phase Langmuir monolayer (LM) of 2-hydroxy-tetracosanoic acid (2-OH TCA), provides a connection between the in-plane rheology of LMs and reversible folding.

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.