Biomechanics of fibroblast-compacted collagen gels investigated under fibrillar framework

Collagen hydrogel spontaneously contracts as fibroblasts are embedded within, a phenomenon widely harnessed in the studies of wound healing process and the creation of engineered tissues. In this study, the mechanical behavior of the cell-collagen gels is distinguished into active contraction process and passive load-deformation process. To investigate the biomechanics in these processes, a fibrillar framework is constituted; which is composed of the single fibrillar force response, the fibrillar network model, and the effects of alterations to the fibrillar network. Quantitative and statistical analysis of these three physical aspects of the framework are conducted, which include the estimation of the number and states of the fibrillar constituents, the probability of the ratio of fibrillar end-to-end distance to the contour length, and the alteration of the statistical parameters for the fibrillar network due to deformation. Through these analyses and the regressions to experimental data, the following results and conclusions are achieved. 1) The traction force exerted by individual fibroblasts during the active contraction can be evaluated by a putative principle, the stationary state of the instantaneous Hamiltonian of the cellular mechanotransduction system; which underlies the cellular response to the change of its mechanical environment 2) The various nonlinear behaviors of the gels in the passive load-deformation process originate from the characteristics of the fibrillar network. These results and conclusions present the most updated understanding to this 3D tissue model

Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors.

Recent experimental evidence points to the possibility that cell surface-associated caveolae may participate in mechanotransduction. The particular shape of caveolae suggests that these structures serve to prevent exposure of putative mechanosensors residing within these membrane invaginations to shear stresses at magnitudes associated with initiation of cell signaling. Accordingly, we numerically analyzed the fluid flow in and around caveolae using the equation of motion for flow of plasma at low Reynolds numbers and assuming no slip-condition on the membrane. The plasma velocity inside a typical caveola and the shear stress acting on its membrane are markedly reduced compared to the outside membrane. Computation of the diffusion field in the vicinity of a caveola under flow, however, revealed a rapid equilibration of agonist concentration in the fluid inside a caveola with the outside plasma. Western blots and immunocytochemistry support the role of caveolae as shear stress shelters for putative membrane-bound mechanoreceptors such as flk-1. Our results, therefore, suggest that caveolae serve to reduce the fluid shear stress acting on receptors in their interior, while allowing rapid diffusion of ligands into the interior. This mechanism may permit differential control of flow and ligand activation of flk-1 receptor in the presence of ligands

Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors.

Recent experimental evidence points to the possibility that cell surface-associated caveolae may participate in mechanotransduction. The particular shape of caveolae suggests that these structures serve to prevent exposure of putative mechanosensors residing within these membrane invaginations to shear stresses at magnitudes associated with initiation of cell signaling. Accordingly, we numerically analyzed the fluid flow in and around caveolae using the equation of motion for flow of plasma at low Reynolds numbers and assuming no slip-condition on the membrane. The plasma velocity inside a typical caveola and the shear stress acting on its membrane are markedly reduced compared to the outside membrane. Computation of the diffusion field in the vicinity of a caveola under flow, however, revealed a rapid equilibration of agonist concentration in the fluid inside a caveola with the outside plasma. Western blots and immunocytochemistry support the role of caveolae as shear stress shelters for putative membrane-bound mechanoreceptors such as flk-1. Our results, therefore, suggest that caveolae serve to reduce the fluid shear stress acting on receptors in their interior, while allowing rapid diffusion of ligands into the interior. This mechanism may permit differential control of flow and ligand activation of flk-1 receptor in the presence of ligands