Microtubule Dynamics Regulate Cyclic Stretch-Induced Cell Alignment in Human Airway Smooth Muscle Cells

Microtubules are structural components of the cytoskeleton that determine cell shape, polarity, and motility in cooperation with the actin filaments. In order to determine the role of microtubules in cell alignment, human airway smooth muscle cells were exposed to cyclic uniaxial stretch. Human airway smooth muscle cells, cultured on type I collagen-coated elastic silicone membranes, were stretched uniaxially (20% in strain, 30 cycles/min) for 2 h. The population of airway smooth muscle cells which were originally oriented randomly aligned near perpendicular to the stretch axis in a time-dependent manner. However, when the cells treated with microtubule disruptors, nocodazole and colchicine, were subjected to the same cyclic uniaxial stretch, the cells failed to align. Lack of alignment was also observed for airway smooth muscle cells treated with a microtubule stabilizer, paclitaxel. To understand the intracellular mechanisms involved, we developed a computational model in which microtubule polymerization and attachment to focal adhesions were regulated by the preexisting tensile stress, pre-stress, on actin stress fibers. We demonstrate that microtubules play a central role in cell re-orientation when cells experience cyclic uniaxial stretching. Our findings further suggest that cell alignment and cytoskeletal reorganization in response to cyclic stretch results from the ability of the microtubule-stress fiber assembly to maintain a homeostatic strain on the stress fiber at focal adhesions. The mechanism of stretch-induced alignment we uncovered is likely involved in various airway functions as well as in the pathophysiology of airway remodeling in asthma

On the singularities of a constrained (incompressible-like) tensegrity-cytoskeleton model under equitriaxial loading

AbstractSingularity theory is applied for the study of the characteristic three-dimensional tensegrity-cytoskeleton model after adopting an incompressibility constraint. The model comprises six elastic bars interconnected with 24 elastic string members. Previous studies have already been performed on non-constrained systems; however, the present one allows for general non-symmetric equilibrium configurations. Critical conditions for branching of the equilibrium are derived and post-critical behaviour is discussed. Classification of the simple and compound singularities of the total potential energy function is effected. The theory is implemented into the cusp catastrophe for the case of one-dimensional branching of the buckling-allowed tensegrity model, and an elliptic umbilic singularity for compound branching of a rigid-bar model. It is pointed out that singularity studies with constraints demand a quite different mathematical approach than those without constraints