Cells in our body utilize a variety of adaptor proteins for transmitting context specific signals that arise from the cellular microenvironment. Adaptor proteins lack enzymatic activity and typically perform their function by acting as scaffolds that bind other signaling proteins. While most adaptor proteins are functionally modulated by biochemical alterations such as phosphorylation, a subset of adaptor proteins are functionally modulated by a mechanical alteration in their structure that makes cryptic sites available for binding to downstream signaling proteins. α-catenin is one such adaptor protein that localizes to cadherin-based cell adhesions by binding the membrane-localized cadherin-β-catenin complex at one side and the cytosolic F-actin on the other side. An increase in actomyosin tension is directly relayed to α-catenin resulting in a change in its conformation making cryptic binding sites accessible to its interacting partners. Here, I describe an updated view of the mechanical regulation of α-catenin in the context of cellular adhesion, including the role of cadherin clustering in its activation.
Determination of left-right asymmetry of the body plan is achieved in the early embryo. At the 4-6 somite stage, a cavity structure, called a node, is observed in the ventral midline surface, in which hundreds of cilia rotate. Nodal cilia are typically tilted toward the posterior and rotate in the clockwise direction, resulting in the generation of leftward flow in the node. Such leftward flow acts as a trigger of left-specific gene expression, and fluid mechanics plays a role in left-right symmetry breaking. To understand the cilia-driven nodal flow, it is necessary to determine the hydrodynamic interactions among rotating cilia, as ciliary motions interact with each other through fluid motion. In this study, we numerically investigated the elastohydrodynamic synchronization of two rotating cilia, as well as the flow field. The ciliary motion was determined by the balance of cytoskeletal elastic force, motor protein-induced active force, and fluid viscous force. According to the geometric clutch hypothesis, the frequency of rotating cilia is controlled by the bending curvature. Owing to hydrodynamic interactions, bending deformations of two cilia become time-dependent, and the rotation is finally locked in anti-phase regardless of the relative position and initial phase difference. By locking in the reverse phase, the average propulsion flow rate becomes 2-3 times larger than in-phase beating. The results of this study form a basis for understanding cilium-driven nodal flow.
Osteoblasts change their intracellular calcium ion concentration in response to mechanical stimuli. Although it has been reported that osteoblasts sense and respond to stretching of a substrate on which osteoblastic cells have adhered, the details of the dynamic characteristics of their calcium signaling response remain unclear. Motion artifacts such as loss of focus during stretch application make it difficult to conduct precise time-course observations of calcium signaling responses. Therefore, in this study, we observed intracellular calcium signaling responses to stretch in a single osteoblastic cell by video rate temporal resolution. Our originally developed cell-stretching microdevice enables in situ observation of a stretched cell without excessive motion artifacts such as focus drift. Residual minor effects of motion artifacts were corrected by the fluorescence ratiometric method with fluorescent calcium indicator Fluo 8H and fluorescent cytoplasm dye calcein red-orange. We succeeded to detect the intracellular calcium signaling response to stretch by video rate temporal resolution. The results revealed a time lag from stretch application to initiation of the intracellular calcium signaling response. We compared two time lags measured at two different cell areas: central and peripheral regions of the cell. The time lag in the central region of the cell was shorter than that in the peripheral region. This result suggests that the osteoblastic calcium signaling response to stretching stimuli initiates around the central region of the cell.
Deformability of epithelial tissues plays a crucial role in embryogenesis, homeostasis, wound healing, and disease. The deformability is determined by the mechanical balance between active force generation and passive response of cells. However, little is known about how multiple cells in epithelial tissues passively respond to external forces. Using a 3D vertex model, we performed computational simulations of longitudinal tension and compression tests of an epithelial tube. Under tension, the tube extended with necking as exhibiting cell rearrangements that play a role in reducing local stiffness of the tube. On the other hand, under compression, the tube buckled with kinking without cell rearrangements. The cell rearrangements occurred when apical and basal cell surfaces stored elastic deformation energies. These results illustrate the variance of deformation modes of epithelial tissues in the single cell level as well as the importance of cell rearrangements in regulating epithelial deformability.
Approximately one in three people over 65 years of age fall each year. The resulting physiological and psychological trauma can lead to physical deconditioning, social isolation and early mortality. Recent research has reported balance recovery can be trained in a single session resulting in dramatic reductions in fall rates. However, most previous research has used repeated exposures to a single hazard in a fixed location and not controlled for reductions in walking speed. It follows, that the biomechanical mechanisms important for reactive balance recovery (in the absence of anticipatory adjustments) are probably not well understood. Here, we investigated the biomechanics of successful reactive balance recovery following the first exposures to unexpected trip and slip hazards in different locations. Ten healthy adults (29.1±5.6 years) completed 32 walks at fixed speed, cadence and step length over a custom 10-meter walkway while being exposed to randomly presented and located slip and trip hazards. Balance recovery kinematics were assessed using a VICON motion analysis system. Repeated exposures to unexpected hazards induced significant reductions (p≤0.05) in anteroposterior (AP) trunk sway following the trips (26.7° to 14.3°; Cohen’s d -1.24) and slips (32.7° to 19.0°; Cohen’s d -0.93). During recovery from unexpected trips, reduced AP trunk sway was strongly correlated with a more posterior centre-of-mass position relative to the stepping foot (r=0.91) and a longer step length (r=-0.71). During recovery from unexpected slips, reduced AP trunk sway was moderately correlated with slower slipping speed (r=0.54) and a less posterior centre-of-mass position relative to the stance (slipping) foot (r=-0.39). The biomechanical mechanisms required for the successful reactive balance recovery from trips and slips were different. Future experimental protocols to optimize reactive balance recovery for fall prevention should therefore use progressive exposures to both slip and trip hazards using specialized equipment and determine if similar biomechanical mechanisms are observed in young and elderly people at risk of falls.