Chitosan Micro-Grooved Membranes with Increased Asymmetry for the Improvement of the Schwann Cell Response in Nerve Regeneration

Peripheral nerve injuries are a common condition in which a nerve is damaged, affecting more than one million people every year. There are still no efficient therapeutic treatments for these injuries. Artificial scaffolds can offer new opportunities for nerve regeneration applications; in this framework, chitosan is emerging as a promising biomaterial. Here, we set up a simple and effective method for the production of micro-structured chitosan films by solvent casting, with high fidelity in the micro-pattern reproducibility. Three types of chitosan directional micro-grooved patterns, presenting different levels of symmetricity, were developed for application in nerve regenerative medicine: gratings (GR), isosceles triangles (ISO) and scalene triangles (SCA). The directional patterns were tested with a Schwann cell line. The most asymmetric topography (SCA), although it polarized the cell shaping less efficiently, promoted higher cell proliferation and a faster cell migration, both individually and collectively, with a higher directional persistence of motion. Overall, the use of micro-structured asymmetrical directional topographies may be exploited to enhance the nerve regeneration process mediated by chitosan scaffolds.

Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3

Epithelial cells organize an ordered array of non-centrosomal microtubules, the minus ends of which are regulated by CAMSAP3. The role of these microtubules in epithelial functions, however, is poorly understood. Here, we show that the kidneys of mice in which Camsap3 is mutated develop cysts at the proximal convoluted tubules (PCTs). PCTs were severely dilated in the mutant kidneys, and they also exhibited enhanced cell proliferation. In these PCTs, epithelial cells became flattened along with perturbation of microtubule arrays as well as of certain subcellular structures such as interdigitating basal processes. Furthermore, YAP and PIEZO1, which are known as mechanosensitive regulators for cell shaping and proliferation, were activated in these mutant PCT cells. These observations suggest that CAMSAP3-mediated microtubule networks are important for maintaining the proper mechanical properties of PCT cells, and its loss triggers cell deformation and proliferation via activation of mechanosensors, resulting in the dilation of PCTs.

Avoiding tensional equilibrium in cells migrating on a matrix with cell-scale stiffness-heterogeneity

Intracellular stresses affect various cell functions, including proliferation, differentiation and movement, which are dynamically modulated in migrating cells through continuous cell-shaping and remodeling of the cytoskeletal architecture induced by spatiotemporal interactions with extracellular matrix stiffness. When cells migrate on a matrix with cell-scale stiffness-heterogeneity, which is a common situation in living tissues, what intracellular stress dynamics (ISD) emerge? In this study, to explore this issue, finite element method-based traction force microscopy was applied to cells migrating on microelastically patterned gels. Two model systems of microelastically patterned gels (stiff/soft stripe and stiff triangular patterns) were designed to characterize the effects of a spatial constraint on cell-shaping and of the presence of different types of cues to induce competing cellular taxis (usual and reverse durotaxis) on the ISD, respectively. As the main result, the prolonged fluctuation of traction stress on a whole-cell scale was markedly enhanced on single cell-size triangular stiff patterns compared with homogeneous gels. Such ISD enhancement was found to be derived from the interplay between the nomadic migration of cells to regions with different degrees of stiffness and domain shape-dependent traction force dynamics, which should be an essential factor for keeping cells far from tensional equilibrium.

A multiscale biophysical model for the recruitment of actin nucleating proteins at the membrane interface

The dynamics and organization of the actin cytoskeleton are crucial to many cellular events such as motility, polarization, cell shaping, and cell division.

Cortical Microtubule Organization during Petal Morphogenesis in Arabidopsis

Cortical microtubules guide the direction and deposition of cellulose microfibrils to build the cell wall, which in turn influences cell expansion and plant morphogenesis. In the model plant Arabidopsis thaliana (Arabidopsis), petal is a relatively simple organ that contains distinct epidermal cells, such as specialized conical cells in the adaxial epidermis and relatively flat cells with several lobes in the abaxial epidermis. In the past two decades, the Arabidopsis petal has become a model experimental system for studying cell expansion and organ morphogenesis, because petals are dispensable for plant growth and reproduction. Recent advances have expanded the role of microtubule organization in modulating petal anisotropic shape formation and conical cell shaping during petal morphogenesis. Here, we summarize recent studies showing that in Arabidopsis, several genes, such as SPIKE1, Rho of plant (ROP) GTPases, and IPGA1, play critical roles in microtubule organization and cell expansion in the abaxial epidermis during petal morphogenesis. Moreover, we summarize the live-confocal imaging studies of Arabidopsis conical cells in the adaxial epidermis, which have emerged as a new cellular model. We discuss the microtubule organization pattern during conical cell shaping. Finally, we propose future directions regarding the study of petal morphogenesis and conical cell shaping.