Exploring the molecular basis for mechanosensation, signal transduction, and cytoskeletal remodeling.

Living cells respond to mechanical stimulation in a variety of ways that affect nearly every aspect of their function. Such responses can range from changes in cell morphology to activation of signaling cascades and changes in cell phenotype. Although the biochemical signaling pathways activated by mechanical stimulus have been extensively studied, little is known of the basic mechanisms by which mechanical force is transduced into a biochemical signal, or how the cell changes its behavior or properties in response to external or internal stresses. One hypothesis is that forces transmitted via individual proteins either at the site of cell adhesion to its surroundings or within the stress-bearing members of the cytoskeleton cause conformational changes that alter their binding affinity to other intracellular molecules. This altered equilibrium state can subsequently either initiate a biochemical signaling cascade or produce more immediate and local structural changes. To understand the phenomena related to mechanotransduction, the mechanics and chemistry of single molecules that form the signal transduction pathways must be examined. This paper presents a range of case studies that seek to explore the molecular basis of mechanical signal sensation and transduction, with particular attention to their macroscopic manifestation in the cell properties, e.g. in focal adhesion remodeling due to local application of force or changes in cytoskeletal rheology and remodeling due to cellular deformation.

Force-induced focal adhesion translocation: effects of force amplitude and frequency.

Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of 5 min with GFP-paxillin while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. A nongraded steady-load threshold for mechanotransduction was established between 0.90 and 1.45 nN. Activation was greatest near the point of forcing (<7.5 microm), indicating that shear forces imposed on the apical cell membrane transmit nonuniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a nonuniform force transmission to basal surface focal adhesion sites. To further understand the role of force transmission on focal adhesion activation and dynamics, sinusoidally varying forces were applied at 0.1, 1.0, 10, and 50 Hz with a 1.45 nN offset and a 2.25 nN maximum. At 10 and 50 Hz, focal adhesion activation did not vary with spatial location, as observed for steady loading, whereas the response was minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, showed tyrosine kinase signaling has a role in force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction.

Denture soft linings: materials available.

Denture soft lining materials are products which are applied to the fitting surfaces of dentures for the purpose of achieving a more equal distribution of load and reduction of local point pressures. These materials have provided a focus for research and controversy for over 100 years. In that time large numbers of products have been advanced as the ideal soft denture liner. This paper discusses the five main groups of materials that have been available to dentists: the natural rubbers, vinyl co-polymers, hydrophilic polymers and the silicone and acrylic based soft lining materials.

Denture soft lining materials: clinical indications.

The success or failure of a soft lining in a denture is dependent not only upon the physical properties of the material employed, but also on an understanding of the intended function of this group of products, and the physiological and biological properties of the resilient oral tissues upon which the denture rests. This paper identifies the clinical factors that must be reviewed in order to assess the need for and likely success of a denture soft lining material.

A computer analysis of condylar movement as determined by cuspal guidances.

In 1926 Hanau proposed a link between incisal, condylar, and occlusal guidances of the stomatognatic system. This work has been extended by undertaking a computer simulation of the movement of the mandible between centric occlusion and centric relation in an effort to establish a possible mathematical relationship between the variables in Hanau's "Quint." One scheme is proposed by which the geometry of the guidances might be analyzed. The results of the analysis show that there could be a direct link between an altered occlusal guidance and one of the factors involved in the initiation of the temporomandibular joint dysfunction syndrome.

A discussion of some factors of relevance to the occlusion of complete dentures.

There exists general agreement that in the construction of complete dentures the accurate positioning of the plane of occlusion is essential for correct denture function. Yet rarely does a prosthodontist give detailed instructions concerning the positioning of this plane to the technician who is to set the teeth. In this paper the three-dimensional location and form of the occlusal plane is discussed. For both anatomical and mechanical reasons the author favours the use of the mandibular rather than the maxillary record rim as the clinical determinant of the level of the artificial occlusion. A change in the method of setting the face-bow is recommended to allow for the difference between the cranial Frankfort plane and the axis-orbital plane of the articulator. Arguments are advanced to support the proposal that artificial teeth should be set to an intercuspal location forward of centric relation; and that the form of the antero-posterior compensating curve of the artificial dentition should be determined by the clinician before the teeth are set to the registration rims.

Sphenotemporalis: a new muscle in man.

A previously unreported human muscle was found in two cadaver specimens. The muscle is situated in the infratemporal fossa and lies superior and deep to the main part of the upper head of the lateral pterygoid muscle. The muscle is attached to the skull on each side of the sphenotemporal suture. Its separated nerve supply arises directly from the trigeminal ganglion. A review of the earlier descriptions of the region shows no previous report and therefore the descriptive name sphenotemporalis is proposed. The possible role and ontogenesis of the muscle are briefly discussed.

A theoretical and clinical investigation into the taper achieved on crown and inlay preparations.

The minimum angles of taper that can in theory be formed to various preparations were established for representative dental preparations and operating distances. These values were compared with the taper of dental preparations formed both under laboratory conditions and in clinical practice, the latter by measurement of taper on the dies of clinically successful crowns and inlays. A possible explanation for the discrepancy noted between recommended degrees of taper and the tapers produced under clinical conditions was considered to be due to the requirement by a dental surgeon to avoid forming undercuts to the line of withdrawal of a cast intracoronal or extracoronal retainer.