Displacement Propagation in Fibrous Networks Due to Local Contraction.

The extracellular matrix provides macroscale structure to tissues and microscale guidance for cell contraction, adhesion, and migration. The matrix is composed of a network of fibers, which each deform by stretching, bending, and buckling. Whereas the mechanics has been well characterized in uniform shear and extension, the response to more general loading conditions remains less clear, because the associated displacement fields cannot be predicted a priori. Studies simulating contraction, such as due to a cell, have observed displacements that propagate over a long range, suggesting mechanisms such as reorientation of fibers toward directions of tensile force and nonlinearity due to buckling of fibers under compression. It remains unclear which of these two mechanisms produces the long-range displacements and how properties like fiber bending stiffness and fiber length affect the displacement field. Here, we simulate contraction of an inclusion within a fibrous network and fit the resulting radial displacements to ur ∼ r-n where the power n quantifies the decay of displacements over distance, and a value of n less than that predicted by classical linear elasticity indicates displacements that propagate over a long range. We observed displacements to propagate over a longer range for greater contraction of the inclusion, for networks having longer fibers, and for networks with lower fiber bending stiffness. Contraction of the inclusion also caused fibers to reorient into the radial direction, but, surprisingly, the reorientation was minimally affected by bending stiffness. We conclude that both reorientation and nonlinearity are responsible for the long-range displacements.

Optometry-based general population survey of pupil ruff atrophy and ocular hypertension.

BACKGROUND: To evaluate and describe the pupil ruff changes and relationship to intraocular pressure, pseudoexfoliation syndrome and glaucoma status in an optometric population in New Zealand. DESIGN: Prospective cross-sectional survey of an optometric population. PARTICIPANTS: Six hundred and twenty subjects over 50 years old routinely attending the participating optometry practices. Exclusion criteria included previous intraocular surgery, ophthalmic laser, uveitis, angle closure and secondary glaucoma. METHODS: Multicentre study involving 11 optometry practices in the Wellington region, New Zealand. The pupillary ruff and associated gonioscopy findings of study participants were graded based on the previously published Pupil Ruff Atrophy grading system. Parameters evaluated include pupillary ruff absence and abnormality, pseudoexfoliation material and trabecular meshwork pigmentation. MAIN OUTCOME MEASURES: Correlations between intereye Pupil Ruff Atrophy grading differences and inter-eye intraocular pressure and cup:disc ratio differences. RESULTS: Six hundred and twenty subjects were included, with a mean age of 62.2 ± 9.1 years and mean intraocular pressure of 14.8 ± 3.4 mmHg. Four hundred and fourteen (66.8%) had bilateral pupil ruff changes and 12 (1.5%) had pseudoexfoliation. Inter-eye intraocular pressure asymmetry was significantly correlated with amount of missing pupillary ruff (r = 0.111; P = 0.022) and trabecular meshwork pigmentation (r = 0.147; P = 0.002). Inter-eye cup:disc ratio asymmetry was not correlated with any of the Pupil Ruff Atrophy grading parameters. CONCLUSIONS: Asymmetry of pupillary ruff absence and trabecular meshwork pigmentation was correlated with intraocular pressure asymmetry (but not with cup:disc ratio asymmetry) in a general optometric population setting in New Zealand.

A cytoskeletal clutch mediates cellular force transmission in a soft, three-dimensional extracellular matrix.

The ability of cells to impart forces and deformations on their surroundings underlies cell migration and extracellular matrix (ECM) remodeling and is thus an essential aspect of complex, metazoan life. Previous work has resulted in a refined understanding, commonly termed the molecular clutch model, of how cells adhering to flat surfaces such as a microscope coverslip transmit cytoskeletally generated forces to their surroundings. Comparatively less is known about how cells adhere to and exert forces in soft, three-dimensional (3D), and structurally heterogeneous ECM environments such as occur in vivo. We used time-lapse 3D imaging and quantitative image analysis to determine how the actin cytoskeleton is mechanically coupled to the surrounding matrix for primary dermal fibroblasts embedded in a 3D fibrin matrix. Under these circumstances, the cytoskeletal architecture is dominated by contractile actin bundles attached at their ends to large, stable, integrin-based adhesions. Time-lapse imaging reveals that α-actinin-1 puncta within actomyosin bundles move more quickly than the paxillin-rich adhesion plaques, which in turn move more quickly than the local matrix, an observation reminiscent of the molecular clutch model. However, closer examination did not reveal a continuous rearward flow of the actin cytoskeleton over slower moving adhesions. Instead, we found that a subset of stress fibers continuously elongated at their attachment points to integrin adhesions, providing stable, yet structurally dynamic coupling to the ECM. Analytical modeling and numerical simulation provide a plausible physical explanation for this result and support a picture in which cells respond to the effective stiffness of local matrix attachment points. The resulting dynamic equilibrium can explain how cells maintain stable, contractile connections to discrete points within ECM during cell migration, and provides a plausible means by which fibroblasts contract provisional matrices during wound healing.