We present a theoretical model to explain recent observations of the orientational response of cells to unidirectional curvature. Experiments show that some cell types when plated on a rigid cylindrical surface tend to reorient their shape and stress fibers along the axis of the cylinder, while others align their stress fibers perpendicular to that axis. Our model focuses on the competition of the shear stress--that results from cell adhesion and active contractility--and the anisotropic bending stiffness of the stress fibers. We predict the cell orientation angle that results from the balance of these two forces in a mechanical equilibrium. The conditions under which the different experimental observations can be obtained are discussed in terms of the theory.

No abstract

DNA molecules in the familiar Watson-Crick double helical B form can be treated as though they have rod-like structures obtained by stacking dominoes one on top of another with each rotated by approximately one-tenth of a full turn with respect to its immediate predecessor in the stack. These "dominoes" are called base pairs. A recently developed theory of sequence-dependent DNA elasticity (Coleman, Olson, & Swigon, J. Chem. Phys. 118:7127-7140, 2003) takes into account the observation that the step from one base pair to the next can be one of several distinct types, each having its own mechanical properties that depend on the nucleotide composition of the step. In the present paper, which is based on that theory, emphasis is placed on the fact that, as each base in a base pair is attached to the sugar-phosphate backbone chain of one of the two DNA strands that have come together to form the Watson-Crick structure, and each phosphate group in a backbone chain bears one electronic charge, two such charges are associated with each base pair, which implies that each base pair is subject to not only the elastic forces and moments exerted on it by its neighboring base pairs but also to long range electrostatic forces that, because they are only partially screened out by positively charged counter ions, can render the molecule's equilibrium configurations sensitive to changes in the concentration c of salt in the medium. When these electrostatic forces are taken into account, the equations of mechanical equilibrium for a DNA molecule with N+1 base pairs are a system of μN nonlinear equations, where μ, the number of kinematical variables describing the relative displacement and orientation of adjacent pairs is in general 6; it reduces to 3 when base-pair steps are assumed to be inextensible and non-shearable. As a consequence of the long-range J Elasticity (2007) 87: electrostatic interactions of base pairs, the μN×μN Jacobian matrix of the equations of equilibrium is full. An efficient numerically stable computational scheme is here presented for solving those equations and determining the mechanical stability of the calculated equilibrium configurations. That scheme is employed to compute and analyze bifurcation diagrams in which c is the bifurcation parameter and to show that, for an intrinsically curved molecule, small changes in c can have a strong effect on stable equilibrium configurations. Cases are presented in which several stable configurations occur at a single value of c.

The response of cells to shear flow is primarily determined by the asymmetry of the external forces and moments that are sensed by each member of a focal adhesion pair connected by a contractile stress fiber. In the theory presented here, we suggest a physical model in which each member of such a pair of focal adhesions is treated as an elastic body subject to both a myosin-activated contractile force and the shear stress induced by the external flow. The elastic response of a focal adhesion complex is much faster than the active cellular processes that determine the size of the associated focal adhesions and the direction of the complex relative to the imposed flow. Therefore, the complex attains its mechanical equilibrium configuration which may change because of the cellular activity. Our theory is based on the experimental observation that focal adhesions modulate their cross-sectional area in order to attain an optimal shear. Using this assumption, our elastic model shows that such a complex can passively change its orientation to align parallel to the direction of the flow.

The statistical mechanics of a short circularized DNA molecule, a DNA minicircle, with a prescribed linking number depends heavily on the mechanical and geometrical properties of the DNA, which are known to be functions of the sequence. A description of a general numerical scheme used for the performed advanced simulation is presented with examples that reveal the effects of sequence dependence and local deformations, caused by protein binding, on the configurations in a canonical ensemble of a supercoiled minicircle. Using a realistic course grain model in which the sequence-dependent elasticity, the intramolecular electrostatic interactions, and the impenetrability of the DNA molecule are taken into account, the bifurcation of equilibria of supercoiled minicircle DNA with the induced bending as a parameter is shown. The unique Monte Carlo scheme for constrained DNA molecules was utilized in order to calculate site-to-site distance probabilities for each pair of sites in the molecule. The simulated examples show not only that the sequence alone can play a significant role in bringing two remote sites to a contact but also the possible existence of several competing regions of contact. The results suggest that the local deformation caused by protein binding can yield a global configurational change, dominated by slithering motion, which brings two (originally) remote sites to close proximity, and that the nature of such effect is related to the sequence architecture.